Histology_Ross

Histology_Ross. Oligodendrocytes appear in specially stained light microscopic preparations as small cells with relatively few processes compared with astrocytes. They are often aligned in rows between axons. Each oligodendrocyte gives off several tonguelike processes that find their way to the axons, where each process wraps itself around a portion of an axon, forming an internodal segment of myelin. The multiple processes of a single oligodendrocyte may myelinate one axon or several nearby axons (Fig. 12.20). The nucleus-containing region of the oligodendrocyte may be at some distance from the axons it myelinates. Because a single oligodendrocyte may myelinate several nearby axons simultaneously, the cell cannot embed multiple axons in its cytoplasm and allow the mesaxon membrane to spiral around each axon. Instead, each tonguelike process appears to spiral around the axon, always staying in proximity to it, until the myelin sheath is formed.


Histology_Ross

Histology_Ross. The myelin sheath in the CNS differs from that in the PNS. There are several other important differences between the myelin sheaths in the CNS and those in the PNS. Oligodendrocytes in the CNS express different myelin-specific proteins during myelination than those expressed by Schwann cells in the PNS. Instead of P0 and PMP-22, which are expressed only in myelin of the PNS, other proteins, including proteolipid protein (PLP), myelin oligodendrocyte glyco protein (MOG), and oligodendrocyte myelin glycoprotein (OMgp), perform similar functions in CNS myelin. Deficiencies in the expression of these proteins appear to be important in the pathogenesis of several autoimmune demyelinating diseases of the CNS.


Histology_Ross

Histology_Ross. Deficiencies in the expression of these proteins appear to be important in the pathogenesis of several autoimmune demyelinating diseases of the CNS. On the microscopic level, myelin in the CNS exhibits fewer Schmidt-Lanterman clefts because the astrocytes provide metabolic support for CNS neurons. Unlike Schwann cells of the PNS, oligodendrocytes do not have an external lamina. Furthermore, because of the manner in which oligodendrocytes form CNS myelin, little or no cytoplasm may be present in the outermost layer of the myelin sheath, and with the absence of external lamina, the myelin of adjacent axons may come into contact. Thus, where myelin sheaths of adjacent axons touch, they may share an intraperiod line. Finally, the nodes of Ranvier in the CNS are larger than those in the PNS. The larger areas of exposed


Histology_Ross

Histology_Ross. FIGURE 12.15 • Electron micrograph of unmyelinated nerve fbers. The individual fibers or axons (A) are engulfed by the cytoplasm of a Schwann cell. The arrows indicate the site of mesaxons. In effect, each axon is enclosed by the Schwann cell cytoplasm, except for the intercellular space of the mesaxon. Other features evident in the Schwann cell are its nucleus (N), the Golgi apparatus (G), and the surrounding basal (external) lamina (BL). In the upper part of the micrograph, myelin (M) of two myelinated nerves is also evident. 27,000. Inset. Schematic diagram showing the relationship of axons engulfed by the Schwann cell. (Reprinted with permission from Barr ML, Kiernan JA. The Human Nervous System. New York: Harper & Row, 1983.) axolemma thus make saltatory conduction (see below) even more efficient in the CNS.


Histology_Ross

Histology_Ross. Another difference between the CNS and the PNS in regard to the relationships between supporting cells and neurons is that unmyelinated neurons in the CNS are often found to be bare—that is, they are not embedded in glial cell processes. The lack of supporting cells around unmyelinated axons as well as the absence of basal lamina material and connective tissue within the substance of the CNS helps to distinguish the CNS from the PNS in histologic sections and in TEM specimens. Microglia possess phagocytotic properties.


Histology_Ross

Histology_Ross. Microglia possess phagocytotic properties. Microglia are phagocytotic cells. They normally account for about 5% of all glial cells in the adult CNS but proliferate and become actively phagocytotic (reactive microglial cells) in regions of injury and disease. Microglial cells are considered part of the mononuclear phagocytotic system (see Folder 6.4, page 185) and originate from granulocyte/monocyte progenitor (GMP) cells. Microglia precursor cells enter the CNS parenchyma from the vascular system. Recent evidence suggests that microglia play a critical role in defense against invading microorganisms and neoplastic cells. They remove bacteria, injured cells, and the debris of cells that undergo apoptosis. They also mediate neuroimmune reactions, such as those occurring in chronic pain conditions.


Histology_Ross

Histology_Ross. Microglia are the smallest of the neuroglial cells and have relatively small, elongated nuclei (Fig. 12.21). When stained with heavy metals, microglia exhibit short, twisted processes. Both the processes and the cell body are covered with numerous spikes. The spikes may be the equivalent of the ruffled border seen on other phagocytotic cells. The TEM reveals numerous lysosomes, inclusions, and vesicles. However, microglia contain little rER and few microtubules or actin filaments. Ependymal cells form the epithelial-like lining of the ventricles of the brain and spinal canal.


Histology_Ross

Histology_Ross. Ependymal cells form the epithelial-like lining of the ventricles of the brain and spinal canal. Ependymal cells form the epithelium-like lining of the fluid-filled cavities of the CNS. They form a single layer of cuboidalto-columnar cells that have the morphologic and physiologic characteristics of fluid-transporting cells (Fig. 12.22). They are tightly bound by junctional complexes located at the apical surfaces. Unlike a typical epithelium, ependymal cells lack an external lamina. At the TEM level, the basal cell surface exhibits numerous infoldings that interdigitate with adjacent astrocyte processes. The apical surface of the cell possesses cilia and microvilli. The latter are involved in absorbing cerebrospinal fluid. Within the system of the brain ventricles, this epithelium-like lining is further modified to produce the cerebrospinal fluid by transport and secretion of materials


Histology_Ross

Histology_Ross. Within the system of the brain ventricles, this epithelium-like lining is further modified to produce the cerebrospinal fluid by transport and secretion of materials FIGURE 12.16 • Photomicrograph of a nerve ganglion. a. Photomicrograph showing a ganglion stained by the Mallory-Azan method. Note the large nerve cell bodies (arrows) and nerve fibers (NF ) in the ganglion. Satellite cells are represented by the very small nuclei at the periphery of the neuronal cell bodies. The ganglion is surrounded by a dense irregular connective tissue capsule (CT ) that is comparable to, and continuous with, the epineurium of the nerve. 200. b. Higher magnification of the ganglion, showing individual axons and a few neuronal cell bodies with their satellite cells (arrows). The nuclei in the region of the axons are mostly Schwann cell nuclei. 640. derived from adjacent capillary loops. The modified ependymal cells and associated capillaries are called the choroid plexus.


Histology_Ross

Histology_Ross. derived from adjacent capillary loops. The modified ependymal cells and associated capillaries are called the choroid plexus. An action potential is an electrochemical process triggered by impulses carried to the axon hillock after other impulses are received on the dendrites or the cell body itself.


Histology_Ross

Histology_Ross. A nerve impulse is conducted along an axon much as a flame travels along the fuse of a firecracker. This electrochemical process involves the generation of an action potential, a wave of membrane depolarization that is initiated at the initial segment of the axon hillock. Its membrane contains a large number of voltage-gated Na and K channels. In response to a stimulus, voltage-gated Na channels in the initial segment of the axon membrane open, causing an influx of Na into the axoplasm. This influx of Na briefly reverses (depolarizes) the negative membrane potential of the resting membrane (70 mV) to positive (30 mV). After depolarization, the voltage-gated Na channels close and voltage-gated K channels open. K rapidly exits the axon, returning the membrane to its resting potential. Depolarization of one part of the membrane sends electrical current to neighboring portions of unstimulated membrane, which is still positively charged. This local current stimulates adjacent portions of


Histology_Ross

Histology_Ross. of one part of the membrane sends electrical current to neighboring portions of unstimulated membrane, which is still positively charged. This local current stimulates adjacent portions of the axon’s membrane and repeats depolarization along the membrane. The entire process takes less than one thousandth of a second. After a very brief (refractory) period, the neuron can repeat the process of generating an action potential once again.


Histology_Ross

Histology_Ross. Rapid conduction of the action potential is attributable to the nodes of Ranvier. Myelinated axons conduct impulses more rapidly than unmyelinated axons. Physiologists describe the nerve impulse as “jumping” from node to node along the myelinated axon. This process is called saltatory (L. saltus, to jump) or discontinuous conduction. In myelinated nerves, the myelin sheath around the nerve does not conduct an electric current and forms an insulating layer around the axon. However, the voltage reversal can only occur at the nodes of Ranvier, where the axolemma lacks a myelin sheath. Here, the axolemma is exposed to extracellular fluids and possesses a high concentration of voltage-gated Na and K channels (see Figs. 12.13 and 12.20). Because of this, the voltage reversal (and, thus, the impulse) jumps as current flows from one node of Ranvier to the


Histology_Ross

Histology_Ross. FIGURE 12.17 • Protoplasmic astrocyte in the gray matter of the brain. a. This schematic drawing shows the foot processes of the protoplasmic astrocyte terminating on a blood vessel and the axonal process of a nerve cell. The foot processes terminating on the blood vessel contribute to the blood–brain barrier. The bare regions of the vessel as shown in the drawing would be covered by processes of neighboring astrocytes, thus forming the overall barrier. b. This laser-scanning confocal image of protoplasmic astrocyte in the gray matter of the dentate gyrus was visualized by intracellular labeling method. In lightly fixed tissue slices, selected astrocytes were impaled and iontophoretically injected with fluorescent dye (AlexaFluor 568) using pulses of negative current. Note the density and spatial distribution of cell processes. 480. (Reprinted with permission from Bushong EA, Martone ME, Ellisman MH. Examination of the relationship between astrocyte morphology and laminar boundaries


Histology_Ross

Histology_Ross. spatial distribution of cell processes. 480. (Reprinted with permission from Bushong EA, Martone ME, Ellisman MH. Examination of the relationship between astrocyte morphology and laminar boundaries in the molecular layer of adult dentate gyrus. J Comp Neurol 2003;462:241–251.)


Histology_Ross

Histology_Ross. FIGURE 12.18 • Fibrous astrocytes in the white matter of the brain. a. Schematic drawing of a fibrous astrocyte in the white mater a bb of the brain. b. Photomicrograph of the white matter of the brain, showing the extensive radiating cytoplasmic processes for which astrocytes are named. They are best visualized, as shown here, with immunostaining methods that use antibodies against GFAP. 220. (Reprinted with permission from Fuller GN, Burger PC. Central nervous system. In: Sternberg SS, ed. Histology for Pathologists. Philadelphia: Lippincott-Raven, 1997.)


Histology_Ross

Histology_Ross. FIGURE 12.19 • Distribution of glial cells in the brain. This diagram shows the three types of glial cells—astrocytes, oligodendrocytes, and microglial cells—interacting with several structures and cells found in the brain tissue. Note that the astrocytes and their processes interact with the blood vessels as well as with axons and dendrites. Note that astrocytes also send their processes toward the brain surface, where they contact the basement membrane of the pia mater, forming the glia limitans. In addition, processes of astrocytes extend toward the fluid-filled spaces in the CNS, where they contact the ependymal lining cells. Oligodendrocytes are involved in myelination of the nerve fibers in the CNS. Microglia exhibit phagocytotic functions. pia mater myelin oligo-dendrocyte ependyma astrocyte microglial cell pericyte neuron nerve fibers myelin axons node of Ranvier (showing axon in contact with extracellular space) oligodendrocyte


Histology_Ross

Histology_Ross. FIGURE 12.20 • Three-dimensional view of an oligodendrocyte as it relates to several axons. Cytoplasmic processes from the oligodendrocyte cell body form flattened cytoplasmic sheaths that wrap around each of the axons. The relationship of cytoplasm and myelin is essentially the same as that of Schwann cells. next. The speed of saltatory conduction is related not only to the thickness of the myelin but also to the diameter of the axon. Conduction is more rapid along axons of greater diameter. In unmyelinated axons, Na and K channels are distributed uniformly along the length of the fiber. The nerve impulse is conducted more slowly and moves as a continuous wave of voltage reversal along the axon. CNS neurons and central glia, except microglial cells, are derived from neuroectodermal cells of the neural tube.


Histology_Ross

Histology_Ross. CNS neurons and central glia, except microglial cells, are derived from neuroectodermal cells of the neural tube. Neurons, oligodendrocytes, astrocytes, and ependymal cells are derived from cells of the neural tube. After developing neurons have migrated to their predestined locations in the neural tube and have differentiated into mature neurons, they no longer divide. However, in the adult mammalian brain, a very small number of cells left from development called neural stem cells retain the ability to divide. These cells migrate into sites of injury and differentiate into fully functional nerve cells. Oligodendrocyte precursors are highly migratory cells. They appear to share a developmental lineage with motor neurons migrating from their site of origin to developing axonal projections (tracts) in the white matter of the brain or


Histology_Ross

Histology_Ross. FIGURE 12.21 • Microglial cell in the gray matter of the brain. a. This diagram shows the shape and characteristics of a microglial cell. Note the elongated nucleus and relatively few processes emanating from the body. b. Photomicrograph of microglial cells (arrows) showing their characteristic elongated nuclei. The specimen was obtained from an individual with diffuse microgliosis. In this condition, the microglial cells are present in large numbers and are readily visible in a routine H&E preparation. 420. (Reprinted with permission from Fuller GN, Burger PC. Central nervous system. In: Sternberg SS, ed. Histology for Pathologists. Philadelphia: Lippincott-Raven, 1997.) spinal cord. The precursors then proliferate in response to the local expression of mitogenic signals. The matching of oligodendrocytes to axons is accomplished through a combination of local regulation of cell proliferation, differentiation, and apoptosis.


Histology_Ross

Histology_Ross. Astrocytes are also derived from cells of the neural tube. During the embryonic and early postnatal stages, immature astrocytes migrate into the cortex, where they differentiate and become mature astrocytes. Ependymal cells are derived from the proliferation of neuroepithelial cells that immediately surround the canal of the developing neural tube. In contrast to other central neuroglia, microglia cells are derived from mesodermal macrophage precursors, specifically from Granulocyte/monocyte progenitor (GMP) cells in bone marrow. They infiltrate the neural tube in the early stages of its development and under the influence of growth factors such as colony stimulating factor-1 (CSF-1) produced by developing neural cells undergo proliferation and differentiation into motile ameboid cells. These motile cells are commonly ob-


Histology_Ross

Histology_Ross. FIGURE 12.22 • Ependymal lining of the spinal canal. a. Photomicrograph of the cental region of the spinal cord stained with toluidine blue. The arrow points to the central canal. 20. b. At higher magnification, ependymal cells, which line the central canal, can be seen to consist of a single layer of columnar cells. 340. (Courtesy of Dr. George D. Pappas.) c. Transmission electron micrograph showing a portion of the apical region of two columnar ependymal cells. They are joined by a junctional complex (JC) that separates the lumen of the canal from the lateral intercellular space. The apical surface of the ependymal cells has both cilia (C) and microvilli (M). Basal bodies (BB) and a Golgi apparatus (G) within the apical cytoplasm are also visible. 20,000. (Courtesy of Dr. Paul Reier.) served in the developing brain. As the only glial cells of mesenchymal origin, microglia possess the vimentin class of intermediate flaments, which can be useful in identifying these cells with


Histology_Ross

Histology_Ross. served in the developing brain. As the only glial cells of mesenchymal origin, microglia possess the vimentin class of intermediate flaments, which can be useful in identifying these cells with immunocytochemical methods.


Histology_Ross

Histology_Ross. PNS ganglion cells and peripheral glia are derived from the neural crest. The development of the ganglion cells of the PNS involves the proliferation and migration of ganglion precursor cells from the neural crest to their future ganglionic sites, where they undergo further proliferation. There, the cells develop processes that reach the cells’ target tissues (e.g., glandular tissue or smooth muscle cells) and sensory territories. Initially, more cells are produced than are needed. Those that do not make functional contact with a target tissue undergo apoptosis.


Histology_Ross

Histology_Ross. Schwann cells also arise from migrating neural crest cells that become associated with the axons of early embryonic nerves. Several genes have been implicated in Schwann cell development. Sex-determining region Y (SRY) box 10 (Sox10) is required for the generation of all peripheral glia from neural crest cells. Axon-derived neuregulin 1 (Nrg-1) sustains the Schwann cell precursors that undergo differentiation and divide along the growing nerve processes. The fate of all immature Schwann cells is determined by the nerve processes with which they have immediate contact. Immature Schwann cells that associate with large-diameter axons mature into myelinating Schwann cells, while those that associate with small-diameter axons mature into nonmyelinating cells. The peripheral nervous system (PNS) consists of peripheral nerves with specialized nerve endings and ganglia containing nerve cell bodies that reside outside the central nervous system.


Histology_Ross

Histology_Ross. The peripheral nervous system (PNS) consists of peripheral nerves with specialized nerve endings and ganglia containing nerve cell bodies that reside outside the central nervous system. A peripheral nerve is a bundle of nerve fibers held together by connective tissue. The nerves of the PNS are made up of many nerve fibers that carry sensory and motor (effector) information between the organs and tissues of the body and the brain and spinal cord. The term nerve fber is used in different ways that can be confusing. It can connote the axon with all of its coverings (myelin and Schwann cell), as used above, or it can connote the axon alone. It is also used to refer to any process of a nerve cell, either dendrite or axon, especially if insufficient information is available to identify the process as either an axon or a dendrite.


Histology_Ross

Histology_Ross. The cell bodies of peripheral nerves may be located within the CNS or outside the CNS in peripheral ganglia. Ganglia contain clusters of neuronal cell bodies and the nerve fibers leading to and from them (see Fig. 12.16). The cell bodies in dorsal root ganglia as well as ganglia of cranial nerves belong to sensory neurons (somatic afferents and visceral afferents that belong to the autonomic nervous system [discussed below]), whose distribution is restricted to specific locations (Table 12.1 and Fig. 12.3). The cell bodies in the paravertebral, prevertebral, and terminal ganglia belong to postsynaptic “motor” neurons (visceral efferents) of the autonomic nervous system (see Table 12.1 and Fig. 12.16). To understand the PNS, it is also necessary to describe some parts of the CNS. Motor neuron cell bodies of the PNS lie in the CNS.


Histology_Ross

Histology_Ross. To understand the PNS, it is also necessary to describe some parts of the CNS. Motor neuron cell bodies of the PNS lie in the CNS. The cell bodies of motor neurons that innervate skeletal muscle (somatic efferents) are located in the brain, brain stem, and spinal cord. The axons leave the CNS and travel in peripheral nerves to the skeletal muscles that they innervate. A single neuron conveys impulses from the CNS to the effector organ. Sensory neuron cell bodies are located in ganglia outside of, but close to, the CNS. In the sensory system (both the somatic afferent and the visceral afferent components), a single neuron connects the receptor, through a sensory ganglion, to the spinal cord or brain stem. Sensory ganglia are located in the dorsal roots of the spinal nerves and in association with sensory components of cranial nerves V, VII, VIII, IX, and X (see Table 12.1). Connective Tissue Components of a Peripheral Nerve


Histology_Ross

Histology_Ross. Connective Tissue Components of a Peripheral Nerve The bulk of a peripheral nerve consists of nerve fibers and their supporting Schwann cells. The individual nerve fibers and their associated Schwann cells are held together by connective tissue organized into three distinctive components, each with specific morphologic and functional characteristics (Fig. 12.23; also, see Fig. 12.3).  The endoneurium includes loose connective tissue sur rounding each individual nerve fiber.  The perineurium includes specialized connective tissue surrounding each nerve fascicle.  The epineurium includes dense irregular connective tis sue that surrounds a peripheral nerve and fills the spaces between nerve fascicles. Endoneurium constitutes the loose connective tissue associated with individual nerve fibers.


Histology_Ross

Histology_Ross. Endoneurium constitutes the loose connective tissue associated with individual nerve fibers. The endoneurium is not conspicuous in routine light microscope preparations, but special connective tissue stains permit its demonstration. At the electron microscope level, collagen fibrils that constitute the endoneurium are readily apparent (see Figs. 12.11 and 12.12). The fibrils run both parallel to, and around, the nerve fibers, binding them together into a fascicle, or bundle. Because fbroblasts are relatively sparse in the interstices of the nerve fibers, it is likely that most of the collagen fibrils are secreted by the Schwann cells. This conclusion is supported by tissue culture studies in which collagen fibrils are formed in pure cultures of Schwann cells and dorsal root neurons.


Histology_Ross

Histology_Ross. Other than occasional fibroblasts, the only other connective tissue cells normally found within the endoneurium are mast cells and macrophages. Macrophages mediate immunologic surveillance and also participate in nerve tissue re-


Histology_Ross

Histology_Ross. TABLE Peripheral Gangliaa12.1 aPractical note: Neuron cell bodies seen in tissue sections such as tongue, pancreas, urinary bladder, and heart are invariably terminal ganglia or “ganglion cells” of the parasympathetic nervous system. Ganglia that contain cell bodies of sensory neurons; these are not synaptic stations  Dorsal root ganglia of all spinal nerves  Sensory ganglia of cranial nerves  Trigeminal (semilunar, Gasserian) ganglion of the trigeminal (V) nerve  Geniculate ganglion of the facial (VII) nerve  Spiral ganglion (contains bipolar neurons) of the cochlear division of the vestibulocochlear (VIII) nerve  Vestibular ganglion (contains bipolar neurons) of the vestibular division of the vestibulocochlear (VIII) nerve  Superior and inferior ganglia of the glossopharyngeal (IX) nerve  Superior and inferior ganglia of the vagus (X) nerve Ganglia that contain cell bodies of autonomic (postsynaptic) neurons; these are synaptic stations  Sympathetic ganglia  Sympathetic


Histology_Ross

Histology_Ross. (IX) nerve  Superior and inferior ganglia of the vagus (X) nerve Ganglia that contain cell bodies of autonomic (postsynaptic) neurons; these are synaptic stations  Sympathetic ganglia  Sympathetic trunk (paravertebral) ganglia (the highest of these is the superior cervical ganglion)  Prevertebral ganglia (adjacent to origins of large unpaired branches of abdominal aorta), including celiac, superior mesenteric, inferior mesenteric, and aorticorenal ganglia  Adrenal medulla, which may be considered a modified sympathetic ganglion (each of the secretory cells of the medulla, as well as the recognizable ganglion cells, is innervated by cholinergic presynaptic sympathetic nerve fibers)  Parasympathetic ganglia  Head ganglia  Ciliary ganglion associated with the oculomotor (III) nerve  Submandibular ganglion associated with the facial (VII) nerve  Pterygopalatine (sphenopalatine) ganglion of the facial (VII) nerve  Otic ganglion associated with the glossopharyngeal (IX) nerve


Histology_Ross

Histology_Ross.  Submandibular ganglion associated with the facial (VII) nerve  Pterygopalatine (sphenopalatine) ganglion of the facial (VII) nerve  Otic ganglion associated with the glossopharyngeal (IX) nerve  Terminal ganglia (near or in wall of organs), including ganglia of the submucosal (Meissner’s) and myenteric (Auerbach’s) plexuses of the gastrointestinal tract (these are also ganglia of the enteric division of the ANS) and isolated ganglion cells in a variety of organs pair. Following nerve injury, they proliferate and actively phagocytose myelin debris. In general, most of the nuclei (90%) found in cross-sections of peripheral nerves belong to Schwann cells; the remaining 10% is equally distributed between the occasional fibroblasts and other cells such as endothelial cells of capillaries, macrophages, and mast cells.


Histology_Ross

Histology_Ross. Perineurium is the specialized connective tissue surrounding a nerve fascicle that contributes to the formation of the blood–nerve barrier.


Histology_Ross

Histology_Ross. Surrounding the nerve bundle is a sheath of unique connective tissue cells that constitutes the perineurium. The perineurium serves as a metabolically active diffusion barrier that contributes to the formation of a blood–nerve barrier. This barrier maintains the ionic milieu of the ensheathed nerve fibers. In a manner similar to the properties exhibited by the endothelial cells of brain capillaries forming the blood–brain barrier (see page 385), perineurial cells possess receptors, transporters, and enzymes that provide for the active transport of substances across perineurial cells. The perineurium may be one or more cell layers thick, depending on the nerve diameter. The cells that compose this layer are squamous; each layer exhibits an external (basal) lamina on both surfaces (Fig. 12.23b and Plate 27, page 390). The cells are contractile and contain an appreciable number of actin filaments, a characteristic of smooth muscle cells and other contractile cells. Moreover, when there


Histology_Ross

Histology_Ross. and Plate 27, page 390). The cells are contractile and contain an appreciable number of actin filaments, a characteristic of smooth muscle cells and other contractile cells. Moreover, when there are two or more perineurial cell layers (as many as five of six layers may be present in larger nerves), collagen fibrils are present between the perineurial cell layers, but fibroblasts are absent. Tight junctions provide the basis for the blood–nerve barrier and are present between the cells located within the same layer of the perineurium. In effect, the arrangement of these cells as a barrier—the presence of tight junctions and external (basal) lamina material—liken them to an epithelioid tissue. On the other hand, their contractile nature and their apparent ability to produce collagen fibrils also liken them to smooth muscle cells and fibroblasts.


Histology_Ross

Histology_Ross. The limited number of connective tissue cell types within the endoneurium (page 375) undoubtedly reflects the protective role that the perineurium plays. Typical immune system cells (i.e., lymphocytes, plasma cells) are not found within the endoneurial and perineurial compartments. This absence of immune cells (other than the mast cells and macrophages) is accounted for by the protective barrier created by the perineurial cells. Typically only fibroblasts, a small number of resident macrophages, and occasional mast cells are present within the nerve compartment. Epine.urium consists of dense irregular connective tissue that surrounds and binds nerve fascicles into a common bundle.


Histology_Ross

Histology_Ross. FIGURE 12.23 • Electron micrograph of a peripheral nerve and its surrounding perineurium. a. Electron micrograph of unmyelinated nerve fibers and a single myelinated fiber (MF). The perineurium (P), consisting of several cell layers, is seen at the left of the micrograph. Perineurial cell processes (arrowheads) have also extended into the nerve to surround a group of axons (A) and their Schwann cell as well as a small blood vessel (BV ). The enclosure of this group of axons represents the root of a small nerve branch that is joining or leaving the larger fascicle. 10,000. The area within the circle encompassing the endothelium of the vessel and the adjacent perineurial cytoplasm is shown in the inset at higher magnification. Note the basal (external) laminae of the vessel and the perineurial cell (arrows). The junction between endothelial cells of the blood vessel is also apparent (arrowheads). 46,000. b. Electron micrograph showing the perineurium of a nerve. Four cellular layers of


Histology_Ross

Histology_Ross. cell (arrows). The junction between endothelial cells of the blood vessel is also apparent (arrowheads). 46,000. b. Electron micrograph showing the perineurium of a nerve. Four cellular layers of the perineurium are present. Each layer has a basal (external) lamina (BL) associated with it on both surfaces. Other features of the perineurial cell include an extensive population of actin microfilaments (MF), pinocytotic vesicles (arrows), and cytoplasmic densities (CD). These features are characteristic of smooth muscle cells. The innermost perineurial cell layer (right) exhibits tight junctions (asterisks) where one cell is overlapping a second cell in forming the sheath. Other features seen in the cytoplasm are mitochondria (M), rough-surfaced endoplasmic reticulum (rER), and free ribosomes (R). 27,000.


Histology_Ross

Histology_Ross. The epineurium forms the outermost tissue of the peripheral nerve. It is a typical dense connective tissue that surrounds the fascicles formed by the perineurium (Plate 28, page 392). Adipose tissue is often associated with the epineurium in larger nerves. The blood vessels that supply the nerves travel in the epineurium, and their branches penetrate into the nerve and travel within the perineurium. Tissue at the level of the endoneurium is poorly vascularized; metabolic exchange of substrates and wastes in this tissue depends on diffusion from and to the blood vessels through the perineurial sheath (see Fig. 12.23). Afferent receptors are specialized structures located at the distal tips of the peripheral processes of sensory neurons. Although receptors may have many different structures, they have one basic characteristic in common: They can initiate a nerve impulse in response to a stimulus. Receptors may be classified as the following.


Histology_Ross

Histology_Ross.  Exteroceptors react to stimuli from the external environment—for example, temperature, touch, smell, sound, and vision.  Enteroceptors react to stimuli from within the body— for example, the degree of filling or stretch of the alimen tary canal, bladder, and blood vessels.  Proprioceptors, which also react to stimuli from within the body, provide sensation of body position and muscle tone and movement. The simplest receptor is a bare axon called a nonencapsulated (free) nerve ending. This ending is found in epithelia, in connective tissue, and in close association with hair follicles. Most sensory nerve endings acquire connective tissue capsules or sheaths of varying complexity.


Histology_Ross

Histology_Ross. Most sensory nerve endings acquire connective tissue capsules or sheaths of varying complexity. Sensory nerve endings with connective tissue sheaths are called encapsulated endings. Many encapsulated endings are mechanoreceptors located in the skin and joint capsules (Krause’s end bulb, Ruffini’s corpuscles, Meissner’s corpuscles, and Pacinian corpuscles) and are described in Chapter 15, Integumentary System (page 501). Muscle spindles are encapsulated sensory endings located in skeletal muscle; they are described in Chapter 11, Muscle Tissue (page 325). Functionally related Golgi tendon organs are encapsulated tension receptors found at musculotendinous junctions. Although the ANS was introduced early in this chapter, it is useful here to describe some of the salient features of its organization and distribution. The ANS is classified into three divisions: The ANS controls and regulates the body’s internal environment.


Histology_Ross

Histology_Ross. The ANS controls and regulates the body’s internal environment. The ANS is the portion of the PNS that conducts involuntary impulses to smooth muscle, cardiac muscle, and glandular epithelium. These effectors are the functional units in the organs that respond to regulation by nerve tissue. The term visceral is sometimes used to characterize the ANS and its neurons, which are referred to as visceral motor (efferent) neurons. However, visceral motor neurons are frequently accompanied by visceral sensory (afferent) neurons that transmit pain and reflexes from visceral effectors (i.e., blood vessels, mucous membrane, and glands) to the CNS. These pseudounipolar neurons have the same arrangement as other sensory neurons—that is, their cell bodies are located in sensory ganglia, and they possess long peripheral and central axons, as described above.


Histology_Ross

Histology_Ross. The main organizational difference between the efferent flow of impulses to skeletal muscle (somatic effectors) and the efferent flow to smooth muscle, cardiac muscle, and glandular epithelium (visceral effectors) is that one neuron conveys the impulses from the CNS to the somatic effector (Fig. 12.24a), whereas a chain of two neurons conveys the impulses from the CNS to the visceral effectors (Fig. 12.24b). Thus, there is a synaptic station in an autonomic ganglion outside the CNS, where a presynaptic neuron makes contact with postsynaptic neurons. Each presynaptic neuron synapses with several post-synaptic neurons. Sympathetic and Parasympathetic Divisions of the Autonomic Nervous System The presynaptic neurons of the sympathetic division are located in the thoracic and upper lumbar portions of the spinal cord.


Histology_Ross

Histology_Ross. The presynaptic neurons of the sympathetic division are located in the thoracic and upper lumbar portions of the spinal cord. The presynaptic neurons send axons from the thoracic and upper lumbar spinal cord to the vertebral and paravertebral ganglia. The paravertebral ganglia in the sympathetic trunk contain the cell bodies of the postsynaptic effector neurons of the sympathetic division (Figs. 12.24b and 12.25). The presynaptic neurons of the parasympathetic division are located in the brain stem and sacral spinal cord. The presynaptic parasympathetic neurons send axons from the brain stem—that is, the midbrain, pons, and medulla, and the sacral segments of the spinal cord (S2 through S4)— to visceral ganglia. The ganglia in or near the wall of abdominal and pelvic organs and the visceral motor ganglia of cranial nerves III, VII, IX, and X contain cell bodies of the postsynaptic effector neurons of the parasympathetic division (Figs. 12.24c and 12.25).


Histology_Ross

Histology_Ross. The sympathetic and parasympathetic divisions of the ANS often supply the same organs. In these cases, the actions of the two are usually antagonistic. For example, sympathetic stimulation increases the rate of cardiac muscle contractions, whereas parasympathetic stimulation reduces the rate.


Histology_Ross

Histology_Ross. Many functions of the SNS are similar to those of the adrenal medulla, an endocrine gland. This functional similarity is partly explained by the developmental relationships between the cells of the adrenal medulla and postsynaptic sympathetic neurons. Both are derived from the neural crest, are innervated by presynaptic sympathetic neurons, and produce closely related physiologically active agents, EPI and NE. A major difference is that the sympathetic neurons deliver the agent directly to the effector, whereas the cells of the adrenal medulla deliver the agent indirectly through the bloodstream. The innervation of the adrenal medulla may constitute an exception to the rule that autonomic innervation consists of a two-neuron chain from the CNS to an effector unless the adrenal medullary cell is considered the functional equivalent of the second neuron (in effect, a neurosecretory neuron). Enteric Division of the Autonomic Nervous System


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Histology_Ross. Enteric Division of the Autonomic Nervous System The enteric division of the ANS consists of the ganglia and their processes that innervate the alimentary canal. The enteric division of the ANS represents a collection of neurons and their processes within the walls of the alimentary canal. It controls motility (contractions of the gut wall), exocrine and endocrine secretions, and blood flow through the gastrointestinal tract; it also regulates immunologic and inflammatory processes.


Histology_Ross

Histology_Ross. The enteric nervous system can function independently from the CNS and is regarded as the “brain of the gut.” However, digestion requires communication between enteric neurons and the CNS, which is provided by parasympathetic and sympathetic nerve fibers. Enteroceptors located in the alimentary tract provide sensory information to the CNS regarding the state of digestive functions. The CNS then coordinates sympathetic stimulation that inhibits gastrointestinal secretion, motor activity, and contraction of gastrointestinal sphincters and blood vessels and parasympathetic stimuli that produce opposite actions. Interneurons integrate information from sensory neurons and relay this information to enteric motor neurons in the form of reflexes. For instance, the gastrocolic reflex is elicited when distention of the stomach stimulates contraction of musculature of the colon, triggering defecation.


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Histology_Ross. Ganglia and postsynaptic neurons of the enteric division are located in the lamina propria, muscularis mucosae, submucosa, muscularis externa, and subserosa of the alimentary canal from the esophagus to the anus (Fig. 12.26). Because the enteric division does not require presynaptic input from the vagus nerve and sacral outflow, sympathetic trunk with paravertebral ganglion splanchnic nerve containing axons of presynaptic neurons


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Histology_Ross. FIGURE 12.24 • Schematic diagram comparing somatic efferent and visceral efferent neurons. a. In the somatic efferent (motor) system, one neuron conducts the impulses from the CNS to the effector (skeletal muscle). b. In the visceral efferent system (repre sented in this diagram by the sympathetic division of the ANS), a chain of two neurons conducts the impulses: A presy naptic neuron located within the CNS and a postsynaptic neuron located in the paravertebral or prevertebral ganglia. Moreover, each presynaptic neuron makes synaptic contact with more than one postsynaptic neuron. Postsy naptic sympathetic fibers supply smooth muscles (as in blood vessels) or glandular epithelium (as in sweat glands). c. Neurons of the ANS that supply organs of the abdomen reach these organs by way of the splanchnic nerves. In this example, the splanchnic nerve joins with the celiac ganglion, where most of the synapses of the two-neuron chain occur. Note that one presynaptic neuron makes contact with


Histology_Ross

Histology_Ross. splanchnic nerves. In this example, the splanchnic nerve joins with the celiac ganglion, where most of the synapses of the two-neuron chain occur. Note that one presynaptic neuron makes contact with several postsynaptic neurons. (Redrawn with permission from Reith EJ, Breidenbach B, Lorenc


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Histology_Ross. M. Textbook of Anatomy and Physiology. St. Louis: CV Mosby, 1978.) blood vessels of visceral structures, blood vessels, sweat glands, and arrector muscles of hairs eye (iris) cephalic arterial ramus carotid periarterial plexus cardiopulmonary splanchnic nerves heart larynx trachea bronchi lungs diaphragm stomach pancreas spleen liver gallbladder bladder penis (clitoris) gonad inferior mesenteric ganglion superior mesenteric ganglion aorticorenal ganglion celiac ganglion abdominopelvic splanchnic nerves large intestine small intestine kidney suprarenal (adrenal) gland rectum internal anal sphincter presynaptic postsynaptic sympathetic fibers lacrimal gland nasal, palatine, and pharyngeal glands eye (iris, ciliary mm.) sacral parasympathetic outflow (via pelvic splanchnic nerves) parotid gland sublingual and submandibular glands heart larynx trachea bronchi lungs liver gallbladder left colic (splenic) flexure dividing sacral para-sympathetic supply from cranial supply large intestine


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Histology_Ross. gland sublingual and submandibular glands heart larynx trachea bronchi lungs liver gallbladder left colic (splenic) flexure dividing sacral para-sympathetic supply from cranial supply large intestine small intestine rectum innervation via sacral outflow innervation via cranial outflow ciliary ganglion bladder penis (clitoris) stomach pancreas pterygopalatine ganglion otic ganglion submandibular ganglion cranial parasympathetic outflow (via 4 cranial nerves) III VII IX X S2 S3 S4


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Histology_Ross. FIGURE 12.25 • Schematic diagram showing the general arrangement of sympathetic and parasympathetic neurons of the ANS. The sympathetic outflow is shown on the right; the parasympathetic, on the left. The sympathetic (thoracolumbar) outflow leaves the CNS from the thoracic and upper lumbar segments (T1–L2 or L3) of the spinal cord. These presynaptic fibers communicate with postsynaptic neurons in two locations, the paravertebral and prevertebral ganglia. Paravertebral ganglia are linked together and form two sympathetic trunks (yellow columns on each side of the spinal cord). Prevertebral ganglia are associated with the main branches of the abdominal aorta (yellow circles). Note the distribution of postsynaptic sympathetic nerve fibers to the viscera. The parasympathetic (craniosacral) outflow leaves the CNS from the gray matter of the brain stem within cranial nerves III, VII, IX, and X and the gray matter of sacral segments (S2–S4) of the spinal cord and is distributed to the


Histology_Ross

Histology_Ross. outflow leaves the CNS from the gray matter of the brain stem within cranial nerves III, VII, IX, and X and the gray matter of sacral segments (S2–S4) of the spinal cord and is distributed to the viscera. The presynaptic fibers traveling with cranial nerves III, VII, and IX communicate with postsynaptic neurons in various ganglia located in the head and neck region (yellow circles). The presynaptic fibers traveling with cranial nerve X and with pelvic splanchnic nerves have their synapses with postsynaptic neurons in the wall of visceral organs (terminal ganglia). The viscera thus contain both sympathetic and parasympathetic innervation. Note that a two-neuron chain carries impulses to all viscera except the adrenal medulla. (Modified from Moore KL, Dalley AF. Clinically Oriented Anatomy. Baltimore: Lippincott Williams & Wilkins, 1999:48–50.) the intestine will continue peristaltic movements even by the same pathologic changes that can occur in neuafter the vagus nerve or pelvic


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Histology_Ross. Baltimore: Lippincott Williams & Wilkins, 1999:48–50.) the intestine will continue peristaltic movements even by the same pathologic changes that can occur in neuafter the vagus nerve or pelvic splanchnic nerves are rons of the brain. Lewy bodies associated with Parkin severed. son’s disease (see Folder 12.1) as well as amyloid plaques


Histology_Ross

Histology_Ross. Neurons of the enteric division are not supported by and neurofibrillary tangles associated with Alzheimer’s Schwann or satellite cells; instead, they are supported by disease have been found in the walls of the large intesenteric neuroglial cells that resemble astrocytes (see tine. This finding may lead to development of routine page 367). Cells of the enteric division are also affected rectal biopsies for early diagnosis of these conditions


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Histology_Ross. FIGURE 12.26 • Enteric nervous system. This diagram shows the organization of the enteric system in the wall of the small intestine. Note the location of two nerve plexuses containing ganglion cells. The more superficial plexus, the myenteric plexus (Auerbach’s plexus), lies between two muscle layers. Deeper in the region of submucosa is a network of unmyelinated nerve fibers and ganglion cells, forming the submucosal plexus (Meissner’s plexus). Parasympathetic fibers originating from the vagus nerve enter the mesentery of the small intestine and synapse with the ganglion cells of both plexuses. Postsynaptic sympathetic nerve fibers also contribute to the enteric nervous system. rather than the more complex and risk-associated biopsy of the brain. A Summarized View of Autonomic Distribution


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Histology_Ross. rather than the more complex and risk-associated biopsy of the brain. A Summarized View of Autonomic Distribution Figures 12.24 and 12.25 summarize the origins and distribution of the ANS. Refer to these figures as you read the descriptive sections. Note that the diagrams indicate both the paired innervation (parasympathetic and sympathetic) common to the ANS as well as the important exceptions to this general characteristic.


Histology_Ross

Histology_Ross. Head  Parasympathetic presynaptic outfow to the head leaves the brain with the cranial nerves, as indicated in Figure 12.25, but the routes are quite complex. Cell bodies may also be found in structures other than head ganglia listed in Table 12.1 and Figure 12.25 (e.g., in the tongue). These are “terminal ganglia” that contain nerve cell bodies of the parasympathetic system. Sympathetic presynaptic outfow to the head comes from the thoracic region of the spinal cord. The postsynaptic neurons have their cell bodies in the superior cervical ganglion; the axons leave the ganglion in a nerve network that hugs the wall of the internal and external carotid arteries to form the periarterial plexus of nerves. The inter nal carotid plexus and external carotid plexus follow the branches of the carotid arteries to reach their destination.


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Histology_Ross.  Parasympathetic presynaptic outfow to the thoracic viscera is via the vagus nerve (X). The postsynaptic neurons have their cell bodies in the walls or in the parenchyma of the organs of the thorax.  Sympathetic presynaptic outfow to the thoracic organs is from the upper thoracic segments of the spinal cord. Sympathetic postsynaptic neurons for the heart are mostly in the cervical ganglia; their axons make up the cardiac nerves. Postsynaptic neurons for the other thoracic viscera are in ganglia of the thoracic part of the sympathetic trunk. The axons travel via small splanchnic nerves from the sympathetic trunk to organs within the thorax and form the pulmonary and esophageal plexuses.


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Histology_Ross.  Parasympathetic presynaptic outfow to the abdominal viscera is via the vagus (X) and pelvic splanchnic nerves. Postsynaptic neurons of the parasympathetic system to abdominopelvic organs are in terminal ganglia that generally are in the walls of the organs, such as the ganglia of the submucosal (Meissner’s) plexus and the myenteric (Auerbach’s) plexus in the alimentary canal. These ganglia are part of the enteric division of the ANS.


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Histology_Ross.  Sympathetic presynaptic outfow to the abdominopelvic organs is from the lower thoracic and upper lumbar segments of the spinal cord. These fibers travel to the prevertebral ganglia through abdominopelvic splanchnic nerves consisting of the greater, lesser, and least thoracic splanchnic and lumbar splanchnic nerves. Postsynaptic neurons have their cell bodies mostly in the prevertebral ganglia (see Fig. 12.24c). Only presynaptic fibers terminating on cells in the medulla of the suprarenal (adrenal) gland originate from paravertebral ganglia of the sympathetic trunk. The adrenal medullary cells function as a special type of postsynaptic neuron that release neurotrans mitter directly into the bloodstream instead of into the synaptic cleft.


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Histology_Ross.  There is no parasympathetic outflow to the body wall and extremities. Anatomically, the autonomic innervation in the body wall is only sympathetic (see Fig. 12.24b). Each spinal nerve contains postsynaptic sympathetic fibers— that is, unmyelinated visceral efferents of neurons whose cell bodies are in paravertebral ganglia of the sympathetic trunk. For sweat glands, the neurotransmitter released by the “sympathetic” neurons is ACh instead of the usual NE. The central nervous system consists of the brain located in the cranial cavity and the spinal cord located in the vertebral canal. The CNS is protected by the skull and vertebrae and is surrounded by three connective tissue membranes called meninges. The brain and spinal cord essentially float in the cerebrospinal fluid that occupies the space between the two inner meningeal layers. The brain is further subdivided into the cerebrum, cerebellum, and brain stem that connects with the spinal cord.


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Histology_Ross. In the brain, the gray matter forms an outer covering or cortex; the white matter forms an inner core or medulla. The cerebral cortex that forms the outermost layer of the brain contains nerve cell bodies, axons, dendrites, and central glial cells, and it is the site of synapses. In a freshly dissected brains, the cerebral cortex has a gray color, hence the name gray matter. In addition to the cortex, islands of gray matter called nuclei are found in the deep portions of the cerebrum and cerebellum.


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Histology_Ross. The white matter contains only axons of nerve cells plus the associated glial cells and blood vessels (axons in fresh preparations appear white). These axons travel from one part of the nervous system to another. Whereas many of the axons going to, or coming from, a specific location are grouped into functionally related bundles called tracts, the tracts themselves do not stand out as delineated bundles. The demonstration of a tract in white matter of the CNS requires a special procedure, such as the destruction of cell bodies that contribute fibers to the tract. The damaged fibers can be displayed by the use of appropriate staining or labeling methods and then traced. Even in the spinal cord, where the grouping of tracts is most pronounced, there are no sharp boundaries between adjacent tracts. Cells of the Gray Matter The types of cell bodies found in the gray matter vary according to which part of the brain or spinal cord is being examined.


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Histology_Ross. Cells of the Gray Matter The types of cell bodies found in the gray matter vary according to which part of the brain or spinal cord is being examined. Each functional region of the gray matter has a characteristic variety of cell bodies associated with a meshwork of axonal, dendritic, and glial processes. The meshwork of axonal, dendritic, and glial processes associated with the gray matter is called the neuropil. The organization of the neuropil is not demonstrable in H&E–stained sections. It is necessary to use methods other than H&E histology to decipher the cytoarchitecture of the gray matter (Plate 29, page 394). Although general histology programs usually do not deal with the actual arrangements of the neurons in the CNS, the presentation of two examples will add to the appreciation of H&E sections that students usually examine. These examples present a region of the cerebral cortex (Fig. 12.27) and the cerebellar cortex (Fig. 12.28), respectively.


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Histology_Ross. The brain stem is not clearly separated into regions of gray matter and white matter. The nuclei of the cranial nerves located in the brain stem, however, appear as islands surrounded by more or less distinct tracts of white matter. The nuclei contain the cell bodies of the motor neurons of the cranial nerves and are both the morphologic and functional counterparts of the anterior horns of the spinal cord. FIGURE 12.27 • Nerve cells in intracortical cerebral circuits. This simple diagram shows the organization and connections between cells in different layers of the cortex contributing to cortical afferent fibers (arrows pointing up) and cortical efferent fibers (arrows pointing down). The small interneurons are indicated in yellow. In other sites in the brain stem, as in the reticular formation, the distinction between white matter and gray matter is even less evident. Organization of the Spinal Cord


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Histology_Ross. In other sites in the brain stem, as in the reticular formation, the distinction between white matter and gray matter is even less evident. Organization of the Spinal Cord The spinal cord is a flattened cylindrical structure that is directly continuous with the brain stem. It is divided into 31 segments (8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal), and each segment is connected to a pair of spinal nerves. Each spinal nerve is joined to its segment of the cord by a number of rootlets grouped as dorsal (posterior) or ventral (anterior) roots (Fig. 12.29; see also Fig. 12.3). In cross-section, the spinal cord exhibits a butterfly-shaped grayish-tan inner substance surrounding the central canal, the gray matter, and a whitish peripheral substance, the white matter (Fig. 12.30). The white matter (see Fig. 12.3) contains only tracks of myelinated and unmyelinated axons traveling to and from other parts of the spinal cord and to and from the brain.


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Histology_Ross. The gray matter contains neuronal cell bodies and their dendrites, along with axons and central neuroglia (Plate 31, ventral ramus of spinal nerve FIGURE 12.28 • Cytoarchitecture of the cerebellar cortex. a.


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Histology_Ross. This diagram shows a section of the folium, a narrow, leaflike gyrus of the cerebellar cortex. Note that the cerebellar cortex contains white matter and gray matter. Three distinct layers of gray matter are identified on this diagram: The superficially located molecular layer, the middle Purkinje cell layer, and the granule cell layer adjacent to the white matter. b. Purkinje cell layer from rat cerebellum visualized using double-fluorescent–labeling methods. Red DNA staining indicates the nuclei of cells in molecular and granular cell layer thin section. Note that each Purkije cell exhibits an abundance of dendrites. 380. (Coutesy of Thomas J. Deerinck.) page 398). Functionally related groups of nerve cell bodies in the gray matter are called nuclei. In this context, the term nucleus means a cluster or group of neuronal cell bodies plus fibers and neuroglia. Nuclei of the CNS are the morphologic and functional equivalents of the ganglia of the PNS. Synapses occur only in the gray


Histology_Ross

Histology_Ross. means a cluster or group of neuronal cell bodies plus fibers and neuroglia. Nuclei of the CNS are the morphologic and functional equivalents of the ganglia of the PNS. Synapses occur only in the gray matter.


Histology_Ross

Histology_Ross. The cell bodies of motor neurons that innervate striated muscle are located in the ventral (anterior) horn of the gray matter. Ventral motor neurons, also called anterior horn cells, are large basophilic cells easily recognized in routine histologic preparations (see Fig. 12.30 and Plate 31, page 398). Because the motor neuron conducts impulses away from the CNS, it is an efferent neuron. The axon of a motor neuron leaves the spinal cord, passes through the ventral (anterior) root, becomes a component of


Histology_Ross

Histology_Ross. The axon of a motor neuron leaves the spinal cord, passes through the ventral (anterior) root, becomes a component of FIGURE 12.29 • Posterior view of the spinal cord with surrounding meninges. Each spinal nerve arises from the spinal cord by rootlets, which merge together to form dorsal (posterior) and ventral (anterior) nerve roots. These roots unite to form a spinal nerve that, after short course, divides into larger ventral (anterior) and smaller dorsal (posterior) primary rami. Note the dura mater (the outer layer of the meninges) surrounds the spinal cord and emerging spinal nerves. The denticulate ligament of the pia mater that anchors the spinal cord to the wall of the spinal canal is also visible. the spinal nerve of that segment, and as such is conveyed to the muscle. The axon is myelinated except at its origin and termination. Near the muscle cell, the axon divides into numerous terminal branches that form neuromuscular junctions with the muscle cell (see page 322).


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Histology_Ross. The cell bodies of sensory neurons are located in ganglia that lie on the dorsal root of the spinal nerve. Sensory neurons in the dorsal root ganglia are pseudounipolar (Plate 27, page 390). They have a single process that divides into a peripheral segment that brings information from the periphery to the cell body and a central segment that carries information from the cell body into the gray matter of the spinal cord. Because the sensory neuron conducts impulses to the CNS, it is an afferent neuron. Impulses are generated in the terminal receptor arborization of the peripheral segment. Connective Tissue of the Central Nervous System Three sequential connective tissue membranes, the meninges, cover the brain and spinal cord.  The dura mater is the outermost layer.  The arachnoid layer lies beneath the dura.  The pia mater is a delicate layer resting directly on the surface of the brain and spinal cord.


Histology_Ross

Histology_Ross. FIGURE 12.30 • Cross-section of the human spinal cord. The photomicrograph shows a cross-section through the lower lumbar (most likely L4–L5) level of the spinal cord stained by the Bielschowsky silver method. The spinal cord is organized into an outer part, the white matter, and an inner part, the gray matter that contains nerve cell bodies and associated nerve fibers. The gray matter of the spinal cord appears roughly in the form of a butterfly. The anterior and posterior prongs are referred to as ventral horns (VH) and dorsal horns (DH), respectively. They are connected by the gray commissure (GC). The white matter contains nerve fibers that form ascending and descending tracts. The outer surface of the spinal cord is surrounded by the pia mater. Blood vessels of the pia mater, the ventral fissure (VF), and some dorsal roots of the spinal nerves are visible in the section. 5.


Histology_Ross

Histology_Ross. Because arachnoid and pia mater develop from the single layer of mesenchyme surrounding the developing brain, they are commonly referred as the pia-arachnoid. In adults, pia mater represents the visceral portion, and arachnoid represents the parietal portion of the same layer. This common origin of pia-arachnoid is evident in adult meninges in which numerous strands of connective tissue (arachnoid trabeculae) pass between pia mater and arachnoid. The dura mater is a relatively thick sheet of dense connective tissue.


Histology_Ross

Histology_Ross. The dura mater is a relatively thick sheet of dense connective tissue. In the cranial cavity, the thick layer of connective tissue that forms the dura mater (L., tough mother) is continuous at its outer surface with the periosteum of the skull. Within the dura mater are spaces lined by endothelium (and backed by periosteum and dura mater, respectively) that serve as the principal channels for blood returning from the brain. These venous (dural) sinuses receive blood from the principal cerebral veins and carry it to the internal jugular veins. Sheetlike extensions of the inner surface of the dura mater form partitions between parts of the brain, supporting those parts within the cranial cavity and carrying the arachnoid to some of the deeper parts of the brain. In the spinal canal, the vertebrae have their own periosteum, and the dura mater forms a separate tube surrounding the spinal cord (see Fig. 12.29).


Histology_Ross

Histology_Ross. The arachnoid is a delicate sheet of connective tissue adjacent to the inner surface of the dura. The arachnoid abuts on the inner surface of the dura and extends delicate arachnoid trabeculae to the pia mater on the surface of the brain and spinal cord. The weblike trabeculae of the arachnoid give this tissue its name (Gr., resembling a spider’s web). Trabeculae are composed of loose connective tissue fibers containing elongated fibroblasts. The space bridged by these trabeculae is the subarachnoid space; it contains the cerebrospinal fuid (Fig. 12.31). The pia matter lies directly on the surface of brain and spinal cord. The pia mater (L., tender mother) is also a delicate connective tissue layer. It lies directly on the surface of the brain and spinal cord and is continuous with the perivascular connective tissue sheath of the blood vessels of the brain and spinal cord. Both surfaces of the arachnoid, the inner FIGURE 12.31 • Schematic diagram of the cerebral meninges.


Histology_Ross

Histology_Ross. FIGURE 12.31 • Schematic diagram of the cerebral meninges. The outer layer, the dura mater, is joined to adjacent bone of the cranial cavity (not shown). The inner layer, the pia mater, adheres to the brain surface and follows all its contours. Note that the pia mater follows the branches of the cerebral arteries as they enter the cerebral cortex. The intervening layer, the arachnoid, is adjacent but not attached to the dura mater. The arachnoid sends numerous, weblike arachnoid trabeculae to the pia mater. Located between the arachnoid and the pia mater is the subarachnoid space; it contains cerebrospinal fluid. The space also contains the larger blood vessels (cerebral arteries) that send branches into the substance of the brain. surface of the pia mater, and the trabeculae are covered with a thin squamous epithelial layer. Both the arachnoid and pia mater fuse around the opening for the cranial and spinal nerves as they exit the dura mater.


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Histology_Ross. The blood–brain barrier protects the CNS from fluctuating levels of electrolytes, hormones, and tissue metabolites circulating in the blood vessels. The observation more than 100 years ago that vital dyes injected into the bloodstream can penetrate and stain nearly all organs except the brain provided the first description of the blood–brain barrier. More recently, advances in microscopy and molecular biology techniques have revealed the precise location of this unique barrier and the role of endothelial cells in transporting essential substances to the brain tissue.


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Histology_Ross. The blood–brain barrier develops early in the embryo through an interaction between glial astrocytes and capillary endothelial cells. The barrier is created largely by the elaborate tight junctions between the endothelial cells, which form continuous-type capillaries. Studies with the TEM using electron-opaque tracers show complex tight junctions between the endothelial cells. Morphologically, these junctions more closely resemble epithelial tight junctions than tight junctions present between other endothelial cells. In addition, TEM studies reveal a close association of astrocytes and their end foot processes with the endothelial basal lamina (Fig. 12.32). The tight junctions eliminate gaps between endothelial cells and prevent simple diffusion of solutes and fluid into the neural tissue. Evidence suggests that the integrity of blood–brain barrier tight junctions depends on normal functioning of the associated astrocytes. In several brain diseases, the blood–brain barrier loses


Histology_Ross

Histology_Ross. Evidence suggests that the integrity of blood–brain barrier tight junctions depends on normal functioning of the associated astrocytes. In several brain diseases, the blood–brain barrier loses effectiveness. Examination of brain tissue in these conditions by TEM reveals loss of the tight junctions as well as alterations in the morphology of astrocytes. Other experimental evidence has revealed that astrocytes release soluble factors that increase barrier properties and tight junction protein content.


Histology_Ross

Histology_Ross. The blood–brain barrier restricts passage of certain ions and substances from the bloodstream to tissues of the CNS. The presence of only a few small vesicles indicates that pinocytosis across the brain endothelial cells is severely restricted. Substances with a molecular weight greater than 500 daltons generally cannot cross the blood–brain barrier. Many molecules that are required for neuronal integrity leave and enter the blood capillaries through the endothelial cells. Thus, O2 and CO2 as well as certain lipid-soluble molecules (e.g., ethanol and steroid hormones) easily penetrate the endothelial cells and pass freely between the blood and extracellular fluid of the CNS. Due to the high K permeability of the neuronal membrane, neurons are particularly sensitive to changes in the concentration of extracellular K. As previously discussed, astrocytes are foot processes of astrocytes FIGURE 12.32 • Schematic drawing of blood–brain barrier.


Histology_Ross

Histology_Ross. FIGURE 12.32 • Schematic drawing of blood–brain barrier. This drawing shows the blood–brain barrier, which consists of endothelial cells joined together by elaborate, complex tight junctions, endothelial basal lamina, and the end foot processes of astrocytes. responsible for buffering the concentration of K in the brain extracellular fluid (page 369). They are assisted by endothelial cells of the blood–brain barrier that effectively limit movement of K into the extracellular fluid of the CNS. Substances that do cross the capillary wall are actively transported by specific receptor-mediated endocytosis. For instance, glucose (which the neuron depends on almost exclusively for energy), amino acids, nucleosides, and vitamins are actively transported by specific transmembrane carrier proteins. The permeability of the blood–brain barrier to these macromolecules is attributable to the level of expression of specific carrier proteins on the endothelial cell surface.


Histology_Ross

Histology_Ross. Several other proteins that reside within the plasma membrane of endothelial cells protect the brain by metabolizing certain molecules, such as drugs and foreign proteins, thus preventing them from crossing the barrier. For example, L-dopa (levodopa), the precursor of the neuromediators dopamine and noradrenaline, easily crosses the blood–brain barrier. However, the dopamine formed from the decarboxylation of L-dopa in endothelial cells cannot cross the barrier and is restricted from the CNS. In this case, the blood–brain barrier regulates the concentration of L-dopa in the brain. Clinically, this restriction explains why L-dopa is administered for the treatment of dopamine deficiency (e.g., Parkinson’s disease) rather than dopamine.


Histology_Ross

Histology_Ross. Recent studies indicate that the end feet of astrocytes also play an important role in maintaining water homeostasis in brain tissue. Water channels (aquaporin AQP4) are found in end foot processes in which water crosses the blood–brain barrier. In pathologic conditions such as brain edema, these channels play a key role in reestablishing osmotic equilibrium in the brain. The midline structures bordering the third and fourth ventricles are unique areas of the brain that are outside the blood–brain barrier.


Histology_Ross

Histology_Ross. Some parts of the CNS, however, are not isolated from substances carried in the bloodstream. The barrier is ineffective or absent in the sites located along the third and fourth ventricles of the brain, which are collectively called circumventricular organs. Circumventricular organs include the pineal gland, median eminence, subfornical organ, area postrema, subcommissural organ, organum vasculosum of the lamina terminalis, and posterior lobe of the pituitary gland. These barrierdeficient areas are most likely involved in sampling of materials circulating in the blood that are normally excluded by the blood–brain barrier and then conveying information about these substances to the CNS. Circumventricular organs are important in regulating body fluid homeostasis and controlling neurosecretory activity of the nervous system. Some researchers describe them as “windows of the brain” within central neurohumoral system.


Histology_Ross

Histology_Ross. Neuronal injury induces a complex sequence of events termed axonal degeneration and neural regeneration. Neurons, Schwann cells, oligodendrocytes, macrophages, and microglia are involved in these responses. In contrast to the PNS, in which injured axons rapidly regenerate, axons severed in the CNS usually cannot regenerate. This striking difference is most likely related to the inability of oligodendrocytes and microglia cells to phagocytose myelin debris quickly and the restriction of large numbers of migrating macrophages by the blood–brain barrier. Because myelin debris contains several inhibitors of axon regeneration, its removal is essential to the regeneration progress. The portion of a nerve fiber distal to a site of injury degenerates because of interrupted axonal transport.


Histology_Ross

Histology_Ross. Degeneration of an axon distal to a site of injury is called anterograde (Wallerian) degeneration (Fig. 12.33, a and b). The first sign of injury, which occurs 8–24 hours after the axon is damaged, is axonal swelling followed by its disintegration. This leads to breakdown of the axonal cytoskeleton. Microtubules, neurofilaments, and other cytoskeleton components are disassembled, resulting in the fragmentation of the axon. This process is known as granular disintegration of the axonal cytoskeleton. In the PNS, loss of axon contact causes dedifferentiation of Schwann cells and breakdown of the myelin sheath that enclosed the axon. Schwann cells downregulate expression of myelin-specific proteins (see page 365) and at the same time upregulate and secrete several glial growth factors (GGFs), members of a family of axon-associated neuregulins and potent stimulators of proliferation. Under the influence of GGFs, Schwann cells divide and arrange themselves in a line along their external


Histology_Ross

Histology_Ross. members of a family of axon-associated neuregulins and potent stimulators of proliferation. Under the influence of GGFs, Schwann cells divide and arrange themselves in a line along their external laminae. Since axonal processes distal to the site of injury have been by phagocytosis, the linear arrangement of the Schwann cells’ external laminae resembles a long tube with an empty lumen (Fig. 12.33b). In the CNS, oligodendrocyte survival is dependent on signals from axons. In contrast to Schwann cells, if oligodendrocytes lose contact with axons, they respond by initiating apoptotic programmed cell death.


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Histology_Ross. The most important cells in clearing myelin debris from the site of nerve injury are monocyte-derived macrophages. In the PNS, even before the arrival of phagocytotic cells at the site of nerve injury, Schwann cells initiate removal of myelin debris. Recent studies demonstrate that resident macrophages (normally present in small numbers in the peripheral nerves) become activated after nerve injury. They migrate to the site of nerve injury, proliferate, and then phagocytize myelin debris.


Histology_Ross

Histology_Ross. The efficient clearance of myelin debris in the PNS is attributed to the massive recruitment of monocyte-derived macrophages that migrate from blood vessels and infiltrate the vicinity of the nerve injury (Fig 12. 34). When an axon is injured, the blood–nerve barrier (see page 376) is disrupted along the entire length of the injured axon, which allows for the influx of these cells into the site of injury. The presence of large numbers of monocyte-derived macrophages speeds up the process of myelin removal, which in peripheral nerves is usually completed within 2 weeks. In the CNS, inefficient clearance of myelin debris due to limited access of monocyte-derived macrophages, the inefficient phagocytic activity of microglia, and the formation of an astrocyte-derived scar severely restrict nerve regeneration.


Histology_Ross

Histology_Ross. A key difference in the CNS response to axonal injury relates to the fact that the blood–brain barrier (see page 385) is disrupted only at the site of injury and not along entire length of the injured axon (see Fig 12.34). This limits infiltration of monocyte-derived macrophages to the CNS and dramatically slows the process of myelin removal, which can take months or even years. Although the number of microglial cells increases at sites of CNS injury, these reactive microglia cells do not possess the full phagocytotic capabilities of migrating macrophages. The inefficient clearance of myelin debris is a major factor in the failure of nerve regeneration in the CNS. Another factor that affects nerve regeneration is the formation of a glial (astrocyte-derived) scar that fills the empty space left by degenerated axons. Scar formation is discussed in Folder 12.3. Traumatic degeneration occurs in the proximal part of the injured nerve.


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Histology_Ross. Traumatic degeneration occurs in the proximal part of the injured nerve. FIGURE 12.33 • Response of a nerve fber to injury. a. A normal nerve fiber at the time of injury, with its nerve cell body and the effector cell (striated skeletal muscle). Note the position of the neuron nucleus and the number and distribution of Nissl bodies.


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Histology_Ross. b. When the fiber is injured, the neuronal nucleus moves to the cell periphery, and the number of Nissl bodies is greatly reduced. The nerve fiber distal to the injury degenerates along with its myelin sheath. Schwann cells dedifferentiate and proliferate; myelin debris are phagocytosed by macrophages. c. Proliferated Schwann cells form cellular cords of Bunger that are penetrated by the growing axonal sprout. The axon grows at a rate of 0.5 to 3 mm/day. Note that the muscle fiber show a pronounced atrophy. d. A confocal immunofluorescent image showing reinnervated skeletal muscle of the mouse. Regenerating motor axons are stained green for neurofilaments reestablished connections with two neuromuscular junctions visualized in pink color, which reflects specific staining for postsynaptic acetylcholine receptors; Schwann cells are stained blue for S100, which represents a Schwann cell–specific calcium-binding protein. Regenerating axons extended along Schwann cells, which led them to


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Histology_Ross. acetylcholine receptors; Schwann cells are stained blue for S100, which represents a Schwann cell–specific calcium-binding protein. Regenerating axons extended along Schwann cells, which led them to the original synaptic sites of the muscle fibers. 640. (Courtesy of Dr. Young-Jin Son.)


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Histology_Ross. Some retrograde degeneration also occurs in the proximal axon and is called traumatic degeneration. This process appears to be histologically similar to antegrade (Wallerian) degeneration. The coverage of traumatic degeneration depends on the severity of the injury and usually extends for only one or a few internodal segments. Sometimes, traumatic degeneration extends more proximally than one or a few nodes of Ranvier and may result in death of the cell body. When a motor fiber is cut, the muscle innervated by that fiber undergoes atrophy (Fig. 12.33c). Retrograde signaling to the cell body of an injured nerve causes a change in gene expression that initiates reorganization of the perinuclear cytoplasm.


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Histology_Ross. Retrograde signaling to the cell body of an injured nerve causes a change in gene expression that initiates reorganization of the perinuclear cytoplasm. Axonal injury also initiates retrograde signaling to the nerve cell body leading to the upregulation of a gene called c-jun. C-jun transcription factor is involved in early as well as later stages of nerve regeneration. Reorganization of the perinuclear cytoplasm and organelles starts within a few days. The cell body of the injured nerve swells, and its nucleus moves peripherally. Initially, Nissl bodies disappear from the center of the neuron and move to the periphery of the neuron in a process called chromatolysis. Chromatolysis is first observed within 1 to 2 days after injury and reaches a peak at about 2 weeks (see Fig. 12.33b). The changes in the cell body are proportional to the amount of axoplasm destroyed by the injury; extensive loss of axoplasm can lead to death of the cell.


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Histology_Ross. Before the development of modern dyes and radioisotope tracer techniques, Wallerian degeneration and chromatolysis were used as research tools. These tools allowed researchers to trace the pathways and destination of axons and the localization of the cell bodies of experimentally injured nerves. In the PNS, Schwann cells divide and develop cellular bands that bridge a newly formed scar and direct growth of new nerve processes. As mentioned above, division of dedifferentiated Schwann cells is the first step in the regeneration of a severed or crushed peripheral nerve. Initially, these cells arrange themselves in a series of cylinders called endoneurial tubes. Removal of myelin failure of axon regeneration


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Histology_Ross. FIGURE 12.34 • Schematic diagram of response to neuronal injury within peripheral and central nervous systems. Injuries of nerve processes (axons and dendrites) both in PNS and CNS induce axonal degeneration and neural regeneration. These processes involve not only neurons but also supportive cells such as Schwann cells and oligodendrocytes, as well as phagocytic cells such as macrophages and microglia. Injuries to axons in PNS lead to their degeneration, which accompanies divisions and dedifferentiation of Schwann cells and disruption of the blood–nerve barrier along entire length of the injured axon. This allows massive infiltration of monocyte-derived macrophages, which are responsible for the process of myelin removal. Rapid clearance of myelin debris allows for axon regeneration and subsequential restoration of blood–nerve barrier. In the CNS, limited disruption of the blood–brain barrier restricts infiltration of monocyte-derived macrophages and dramatically slows the process of


Histology_Ross

Histology_Ross. restoration of blood–nerve barrier. In the CNS, limited disruption of the blood–brain barrier restricts infiltration of monocyte-derived macrophages and dramatically slows the process of myelin removal. In addition, appoptosis of oligodendrocytes, an inefficient phagocytic activity of microglia, and the formation of an astrocyte-derived scar lead to failure in nerve regeneration in the CNS.


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Histology_Ross. and axonal debris from inside the tubes causes them to eventu-They preferentially interact with proteins of the extracellular ally collapse. Proliferating Schwann cells organize themselves matrix such as fibronectin and laminin found within the into cellular bands resembling longitudinal columns called external lamina of the Schwann cell. Thus, if a sprout associates bands of Bungner. Cellular bands guide the growth of new itself with a band of Bungner, it regenerates between the layers nerve processes (neurites or sprouts) of regenerating axons. of external lamina of the Schwann cell. This sprout will grow Once the bands are in place, large numbers of sprouts begin to along the band at a rate of about 3 mm per day. Although many grow from the proximal stump (see Fig. 12.33c). A growth new sprouts do not make a contact with cellular bands and decone develops in the distal portion of each sprout that consists generate, their large number increases the probability of of filopodia rich


Histology_Ross

Histology_Ross. sprouts do not make a contact with cellular bands and decone develops in the distal portion of each sprout that consists generate, their large number increases the probability of of filopodia rich in actin filaments. The tips of the filopodia reestablishing sensory and motor connections. After crossing establish a direction for the advancement of the growth cone. the site of injury, sprouts enter the surviving cellular bands in  FOLDER 12.3 Clinical Correlation: Reactive Gliosis: Scar Formation in the CNS


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Histology_Ross. When a region of the CNS is injured, astrocytes near the leasion become activated. They divide and undergo marked hypertrophy with a visible increase in the number of their cytoplasmic processes. In time, the processes be-come densly packed with GFAP intermediate fla-ments. Eventually, scar tissue is formed. This process is referred to as reactive gliosis, while the resulting per-manent scar is most often called a plaque. Reactive glio-sis varies widely in duration, degree of hyperplasia, and time course of expression of GFAP immunostaining. Se-veal biological mechanisms for induction and mainte-nance of reactive gliosis have been proposed. The type of glial cell that responds during reactive gliosis depends on the brain structure that is damagd. In addition, activation of microglial cell population occurs almost immedietaly after any kind of injury to the CNS. These reactive mi-croglial cells migrate toward the site of injury and exhibit marked phagocitic activity. However, their


Histology_Ross

Histology_Ross. population occurs almost immedietaly after any kind of injury to the CNS. These reactive mi-croglial cells migrate toward the site of injury and exhibit marked phagocitic activity. However, their phagocitic ac-tivity and ability to remove myelin debris is much less than that of monocyte-derived macrophages. Gliosis is a prominent feature of many diseases of the CNS, includ-ing stroke, neurotoxic damage, genetic diseases, inflam-matory demyelination, and neurodegenerative disorders such as multiple sclerosis. Much of the research in CNS regeneration is focused on preventing or inhibiting glial scar formation.


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Histology_Ross. the distal stump. These bands then guide the neurites to their destination as well as provide a suitable microenvironment for continued growth (Fig. 12.33d). Axonal regeneration leads to Schwann cell redifferentiation, which occurs in a proximal-todistal direction. Redifferentiated Schwann cells upregulate genes for myelin-specific proteins and downregulate c-jun. If physical contact is reestablished between a motor neuron and its muscle, function is usually reestablished.


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Histology_Ross. If physical contact is reestablished between a motor neuron and its muscle, function is usually reestablished. Microsurgical techniques that rapidly reestablish intimate apposition of severed nerve and vessel ends have made reat tachment of severed limbs and digits, with subsequent reestablishment of function, a relatively common procedure. If the axonal sprouts do not reestablish contact with the appropriate Schwann cells, then the sprouts grow in a disorganized manner, resulting in the mass of tangled axonal processes known as traumatic neuroma or amputation neuroma. Clinically, traumatic neuroma usually appears as a freely movable nodule at the site of nerve injury and is characterized by pain, particularly on palpation. Traumatic neuroma of the injured motor nerve prevents reinnervation of the affected muscle.


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Histology_Ross. Ganglia are clusters of neuronal cell bodies located outside the central nervous system (CNS); nerve fibers lead to and from them. Sensory ganglia lie just outside the CNS and contain the cell bodies of sensory nerves that carry impulses into the CNS. Autonomic ganglia are pe-ripheral motor ganglia of the autonomic nervous system (ANS) and contain the cell bodies of postsynaptic neurons that conduct nerve im-pulses to smooth muscle, cardiac muscle, and glands. Synapses between presynaptic neurons (all of which have their cell bodies in the CNS) and postsynaptic neurons occur in autonomic ganglia. Sympathetic ganglia constitute a major subclass of autonomic ganglia; parasym-pathetic ganglia and enteric ganglia constitute the other subclasses. Sympathetic ganglia are located in the sympathetic chain (paravertebral ganglia) and on the anterior surface of the aorta (prevertebral ganglia). They send long postsynaptic axons to the viscera. Parasympathetic ganglia (terminal ganglia) are


Histology_Ross

Histology_Ross. chain (paravertebral ganglia) and on the anterior surface of the aorta (prevertebral ganglia). They send long postsynaptic axons to the viscera. Parasympathetic ganglia (terminal ganglia) are located in, or close to, the or-gans innervated by their postsynaptic neurons. The enteric ganglia are located in the submucosal plexus and the myenteric plexus of the ali-mentary canal. They receive parasympathetic presynaptic input as well as intrinsic input from other enteric ganglia and innervate smooth muscle of the gut wall.


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Histology_Ross. Sympathetic ganglion, human, silver and H&E stains ×160. A sympathetic ganglion stained with silver and counter-stained with H&E is illustrated here. Shown to advantage are several discrete bundles of nerve fibers (NF) and numerous large circular structures, namely, the cell bodies (CB) of the postsynaptic neurons. Random patterns of nerve fibers are also seen. Moreover, careful examination of the cell bodies shows that some display several processes joined to them. Thus, these are multipolar neurons (one contained within the rectangle is shown at higher magnification). Generally, the connective tissue is not conspicuous in a silver preparation, although it can be identified by virtue of its location about the larger blood vessels (BV), particularly in the upper part of this figure.


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Histology_Ross. PLATE 27 • SYM PATH ETIC AN D DORSAL ROOT GANG LIA KEY A, axon BV, blood vessels CB, cell body of neuron CT, connective tissue L, lipofuscin N, nucleus of nerve cell NF, nerve fibers NL, nucleolus P, processes of nerve cell body Sat C, satellite cells arrowheads, neurilemma asterisks, clusters of satellite cells Sympathetic ganglion, human, silver and H&E stains ×500.


Histology_Ross

Histology_Ross. Sympathetic ganglion, human, silver and H&E stains ×500. The cell bodies of the sympathetic ganglion are typically large, and the one labeled here shows several processes (P). In addition, the cell body contains a large, pale-staining spherical nucleus (N); this, in turn, contains a spherical, intensely staining nucleolus (NL). These features, namely, a large pale-staining nucleus (indicating much-extended chromatin) and a large nucleolus, reflect a cell active in protein synthesis. Also shown in the cell body are accumulations of lipofuscin (L), a yellow pigment that is darkened by the silver. Because of the large size of the cell body, the nucleus is not always included in the section; in that case, the cell body appears as a rounded cytoplasmic mass. Dorsal root ganglion, cat, H&E ×160.


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Histology_Ross. Dorsal root ganglion, cat, H&E ×160. Dorsal root ganglia differ from autonomic ganglia in a number of ways. Whereas the latter contain multipolar neurons and have synaptic connections, dorsal root ganglia contain pseudounipolar sensory neurons and have no synaptic connections in the ganglion. Part of a dorsal root ganglion stained with H&E is shown in this figure. The specimen includes the edge of the ganglion, where it is covered with connective tissue (CT). The dorsal root ganglion contains large cell bodies (CB) that are typically arranged as closely packed clusters. Also, between and around the cell clusters, there are bundles of nerve fibers (NF). Most of the fiber bundles indicated by the label have been sectioned longitudinally. Dorsal root ganglion, cat, H&E ×350.


Histology_Ross

Histology_Ross. Dorsal root ganglion, cat, H&E ×350. At higher magnification of the same ganglion, the constituents of the nerve fiber show their characteristic structure, namely, a centrally located axon (A) surrounded by a myelin space (not labeled), which, in turn, is bounded on its outer border by the thin cytoplasmic strand of the neurilemma (arrowheads). The cell bodies of the sensory neurons display large, pale-staining spherical nuclei (N) and intensely staining nucleoli (NI). Also seen in this H&E preparation are the nuclei of satellite cells (Sat C) that completely surround the cell body and are continuous with the Schwann cells that invest the axon. Note how much smaller these cells are than the neurons. Clusters of cells (asterisks) within the ganglion that have an epithelioid appearance are en face views of satellite cells where the section tangentially includes the satellite cells but barely grazes the adjacent cell body.


Histology_Ross

Histology_Ross. Peripheral nerves are composed of bundles of nerve fibers held together by connective tissue and a specialized layer (or layers) of cells, the perineurium. The connective tissue consists of an outer layer, the epineurium, surrounding the whole nerve; the perineurium, surrounding bundles of nerve fibers; and the endoneurium, associated with individual neurons. Each nerve fiber consists of an axon that is surrounded by a cellular investment called the neurilemma, or the sheath of Schwann. The fiber may be myelinated or unmyelinated. The myelin, if present, is immediately around the axon and is formed by the concentric wrapping of the Schwann cell around the axon. This, in turn, is surrounded by the major portion of the cytoplasm of the Schwann cell, forming the neurilemma. Unmyelinated axons rest in grooves in the Schwann cell. Peripheral nerve, cross-section, femoral nerve, H&E. ×200 and 640


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Histology_Ross. Peripheral nerve, cross-section, femoral nerve, H&E. ×200 and 640 This cross-section shows several bundles of nerve fibers (BNF). The external cover for the entire nerve is the epineurium (Epn), the layer of dense connective tissue that one touches when a nerve has been exposed during a dissection. The epineurium may also serve as part of the outermost cover of individual bundles. It contains blood vessels (BV) and may contain some fat cells. Typically, adipose tissue (AT) is found about the nerve. Figure on right shows, at higher magnification, the perineurial septum (marked with arrows on left image, which is now rotated and vertically disposed (arrows)).


Histology_Ross

Histology_Ross. Figure on right shows, at higher magnification, the perineurial septum (marked with arrows on left image, which is now rotated and vertically disposed (arrows)). The layer under the epineurium that directly surrounds the bundle of nerve fibers is the perineurium (Pn). As seen in the cross-section through the nerve, the nuclei of the perineurial cells appear flat and elongate; they are actually being viewed on edge and belong to flat cells that are also being viewed on edge. Again, as noted by the distribution of nuclei, it can be ascertained that the perineurium is only a few cells thick. The perineurium is a specialized layer of cells and extracellular material whose arrangement is not evident in H&E sections. The perineurium (Pn) and epineurium (Epn) are readily distinguished in the triangular area formed by the diverging perineurium of the two adjacent nerve bundles.


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Histology_Ross. The nerve fibers included in Figure on right are mostly myelinated, and because the nerve is cross-sectioned, the nerve fibers are also seen in this plane. They have a characteristic cross-sectional profile. Each nerve fiber shows a centrally placed axon (A); this is surrounded by a myelin space (M) in which some radially disposed precipitate may be retained, as in this specimen. External to the myelin space is a thin cytoplasmic rim representing the neurilemma. On occasion, a Schwann cell nucleus (SS ) appears to be perched on the neurilemma. As shown in the illustration, the upper edge of the nuclear crescent appears to occupy the same plane as that occupied by the neurilemma (N). These features enable one to identify the nucleus as belonging to a Schwann (neurilemma) cell. Other nuclei are not related to the neurilemma but, rather, appear to be between the nerve fibers. Such nuclei belong to the rare fibroblasts (F) of the endoneurium. The latter is the delicate connective tissue


Histology_Ross

Histology_Ross. are not related to the neurilemma but, rather, appear to be between the nerve fibers. Such nuclei belong to the rare fibroblasts (F) of the endoneurium. The latter is the delicate connective tissue between the individual nerve fibers; it is extremely sparse and contains the capillaries (C) of the nerve bundle.


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Histology_Ross. Peripheral nerve, longitudinal section, femoral nerve, H&E. ×200 and 640


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Histology_Ross. The edge of a longitudinally sectioned nerve bundle is shown on left; a portion of the same nerve bundle is shown at higher magnification on right image. The boundary between the epineurium (Epn) and perineurium is ill-defined. Within the nerve bundle, the nerve fibers show a characteristic wavy pattern. Included among the wavy nerve fibers are nuclei belonging to Schwann cells and to cells within the endoneurium. Higher magnification allows one to identify certain specific components of the nerve. Note that the nerve fibers (NF) are now shown in longitudinal profile. Moreover, each myelinated nerve fiber shows a centrally positioned axon (A) surrounded by a myelin space (M), which, in turn, is bordered on its outer edge by the thin cytoplasmic band of the neurilemma cell (NI). Another diagnostic feature of myelinated nerve fibers is also seen in longitudinal section, namely, the node of Ranvier (NR). This is where the ends of the two Schwann cells meet. Histologically, the node


Histology_Ross

Histology_Ross. diagnostic feature of myelinated nerve fibers is also seen in longitudinal section, namely, the node of Ranvier (NR). This is where the ends of the two Schwann cells meet. Histologically, the node appears as a constriction of the neurilemma, and sometimes, the constriction is marked by a cross-band, as in figure on right. It is difficult to determine whether the nuclei (N) shown here belong to Schwann cells or to endoneurial fibroblasts.


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Histology_Ross. KEY A, axon AT, adipose tissue BNF, bundle of nerve fibers BV, blood vessels C, capillary Epn, epineurium F, fibroblast M, myelin N, nucleus of Schwann cell NF, nerve fiber Nl, neurilemma NR, node of Ranvier Pn, perineurium SS, Schwann cell nucleus arrows, septum formed by perineurium The cerebrum is the principal portion of the brain and contains the cell bodies of nerves that receive and store sensory information, nerves that control voluntary motor activity, and nerves that integrate and coordinate the activity of other nerves, as well as the nerves and neural pathways that constitute memory. Cerebral cortex, brain, human, Luxol fast blue-PAS ×65.


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Histology_Ross. This micrograph shows a low-magnification view of the cerebral cortex (CC). It includes the full thickness of the gray matter and a small amount of white matter at the bottom of the micrograph (WM). The white matter contains considerably fewer cells per unit area; these are neuroglial cells rather than nerve cell bodies that are present in the cortex. Covering the cortex is the pia mater (PM). A vein (V) can be seen enclosed by the pia mater. Also, a smaller blood vessel (BV) can be seen entering the substance of the cortex. The six layers of the cortex are marked by dashed lines, which represent only an approximation of the 394 boundaries. Each layer is distinguished on the basis of predominant cell types and fiber (axon and dendrite) arrangement. Unless the fibers are specifically stained, they cannot be utilized to further aid in identification of the layers. Rather, the delineation of the layers, as they are identified here, is based on cell types, and more specifically, the shape


Histology_Ross

Histology_Ross. they cannot be utilized to further aid in identification of the layers. Rather, the delineation of the layers, as they are identified here, is based on cell types, and more specifically, the shape and appearance of the cells. The six layers of the cortex are named and described as follows:


Histology_Ross

Histology_Ross. I: The plexiform layer (or molecular layer) consists largely of fibers, most of which travel parallel to the surface, and relatively few cells, mostly neuroglial cells and occasional horizontal cells of Cajal. II: The small pyramidal cell layer (or outer granular layer) consists mainly of small pyramidal cells, and granule cells, also called stellate cells. III: The layer of medium pyramidal cells (or layer of outer pyramidal cells) is not sharply demarcated from layer II. However, the pyramidal cells are somewhat larger and posses a typical pyramidal shape. IV: The granular layer (or inner granular layer) is characterized by the presence of many small granule cells (stellate cells). V: The layer of large pyramidal cells (or inner layer of pyramidal cells) contains pyramidal cells that, in many parts of the cerebrum, are smaller than the pyramidal cells of layer III but in the motor area are extremely large and are called Betz cells.