Histology Ch 12 382-389
Organization of Nervous System
-CNS consists of brain and spinal cord; protected by skull, vertebrae, and 3 layers of meninges
-brain/spinal cord float in CSF between the two inner meningeal layers
-brain is divided into cerebrum, cerebellum, brain stem
-in brain, gray matter forms the outer covering (cortex), and white matter forms inner core
-the cerebral cortex contains cell bodies, axons, dendrites, glia, and synapses and has a gray
color, called gray matter
-islands of gray matter called nuclei are found in deep portions of cerebrum and cerebellum
-white matter has only axons of nerve cells and glia + blood vessels
-axons are bundled into functionally related groups called tracts without boundaries
Cells of the Gray Matter – types of cells vary depending where they are found
-each functional region of gray matter has characteristic variety of cell bodies associated with a
meshwork of axonal, dendritic, and glial processes, called the neuropil
-the brain stem is not separated into regions of gray matter and white matter except for the
nuclei of cranial nerve cell bodies, which are morphologic and functional counterparts to
anterior horns of spinal cord
-in the reticular formation in brain stem, distinction between white/gray matter is less evident
Organization of the Spinal Cord – spinal cord is a flat cylinder continuous w/ brainstem and is
divided into 31 segments (8C, 12T, 5L, 5S, and 1 Coccygeal). Each segment is connected to a pair
of spinal nerves joined to cord by rootlets grouped as dorsal or ventral
-in cross section, cord is butterfly-shaped with gray matter interior around a central canal of
gray matter with white matter in the periphery (contains only tracts of axons)
-the gray matter contains neuronal cell bodies and dendrites with axons and neuroglia
-functionally related groups of cell bodies are called nuclei
-CNS nuclei are equivalents of PNS ganglia
-Cell bodies of motor neurons that innervate striated muscle are in ventral horn
-ventral motor neurons are basophilic, efferent neurons
-axon leaves spinal cord, passes ventral root to join spinal nerve  muscle
-axon is myelinated EXCEPT at its origin and termination
-near muscle cell, axon divides into numerous terminal branches that form
neuromuscular junctions with muscle cell
-cell bodies of sensory neurons are in ganglia that lie on dorsal root of spinal nerve
-sensory neurons in dorsal root ganglia (DRG) are PSEUDOUNIPOLAR – single process that
divides into PERIPHERAL segment to bring info from periphery to cell body, and a CENTRAL
segment that carries info from cell body to gray matter of spinal cord
-these are afferent neurons
Connective Tissue of CNS – three layers of meninges:
-dura mater – outermost
-arachnoid – underneath dura
-pia mater – rests directly on surface of brain and spinal chord
-arachnoid and pia mater develop from 1 layer of mesenchyme – referred to as pia-arachnoid
-in adults, pia is the visceral layer and arachnoid is the parietal portion of layer
-evident in adult meninges where many CT strands (arachnoid trabeculae) pass
-Dura mater is thick sheet of dense connective tissue (CT) – in skull, the dura mater is
continuous at its outer surface with periostium of skull
-inside the dura are spaces lined by endothelium to serve as venous sinuses that drain blood
returning from the brain into the INTERNAL jugular veins
-vertebrae have their own periostium and dura forms separate tube surrounding cord
Arachnoid is a Delicate Sheet of CT adjacent to inner surface of dura
-arachnoid is on inner surface of dura and extends arachnoid trabeculae to pia mater in brain
and spinal cord
-web-like trabeculae give arachnoid its name
-trabeculae are composed of LOOSE CT fibers with elongated fibroblasts
-trabeculae bridges the subarachnoid space (contains CSF)
Pia Mater lies on surface of brain and spinal cord – CT layer that is continuous with perivascular
CT of sheath of blood vessels of brain and spinal cord
-the inner surface pia mater, both sides of arachnoid matter, and trabeculae are covered with
SQUAMOUS EPITHELIUM
-arachnoid and pia mater fuse around opening for cranial and spinal nerve as they exit dura
Blood-Brain Barrier (BBB) – protects CNS from fluctuating levels of electrolytes, hormones, and
tissue metabolites circulating in blood
-develops in embryo through interaction of astrocytes and capillary endothelial cells
-the barrier is created by tight junctions between endothelial cells, which form continuous-type
capillaries
-studies reveal association of astrocytes and their foot processes with endothelial basal lamina
-integrity of barrier depends on normal functioning of astrocytes
-tight junctions prevent diffusion of solutes and fluid into neural tissue
BBB restricts passage of certain ions and substances from bloodstream to CNS – few numbers
of vesicles indicates pinocytosis across endothelial cells is restricted
-substances of molecular weight 500 daltons CANNOT cross BBB
-O2, CO2, and lipid-soluble molecules (ethanol, steroids) EASILY cross BBB
-neuronal membrane highly permeable to K+, so neurons are sensitive to extracellular changes
in postassium
-astrocytes buffer K concentration in brain extracellular fluid and are assisted by
endothelial cells of BBB that limit K movement into CNS extracellular fluid
-substances that can cross capillary wall are actively transported by receptor-mediated
endocytosis (glucose, amino acids, nucleosides, and vitamins) by specific membrane carrier
proteins on endothelial cells
-L-dopa (precursor to dopamine and noradrenaline) crosses BBB, but dopamine fromed
by decarboxylation of L-dopa CANNOT cross BBB and is restricted from CNS
-End feet of astrocytes also play a role in water homeostasis
-water channels (aquaporin AQP4) found in end foot processes in which water crosses
BBB; in brain edema, these channels reestablish osmotic equilibrium
-The midline structures bordering third and fourth ventricles are unique areas of brain outside
the BBB – some parts of CNS not isolated from substances in bloodstream, such as in these
areas near 3rd and 4th ventricle, collectivelt called the circumventricular organs – include the
pineal gland, median eminence, subfornical organ, area postrema, subcommissural organ,
organum vasculosum of lamina terminalis, and posterior pituitary
-these areas sample substances in blood and convey info to CNS
-Circumventricular organs are important in regulating fluid homeostasis and controlling
neurosecretory activity
Response of Neurons to Injury – injury induces axonal degeneration and neural regeneration;
in the PNS, axons can rapidly regenerate, but in CNS, axons cannot usually regenerate
-most likely related to inability of oligodendrocytes and microglia to phagocytose myelin debris
quickly and the restriction of large numbers of migrating macrophages by BBB
-myelin debris contains inhibitors of axon regeneration, and needs to be removed
Degeneration – portion of a nerve fiber distal to site of injury degenerates due to interrupted
transport, called anterograde (Wallerian) degeneration
-first sign of injury is axonal swelling followed by disintegration  breakdown of microtubules,
neurofilaments to result in fragmentation of axon; known as granular disintegration of axonal
cytoskeleton
-in PNS, loss of axon contact causes dedifferentiation of Schwann cells and breakdown
of myelin sheath around axon; Schwann cells upregulate glial growth factors (GGFs)
which stimulate axon regeneration
-under influence of GGFs, schwann cells divide and arrange themselves in a line alone their
external laminae
-resembles a long tube with empty lumen
-in CNS, oligodendrocyte survival is dependent on signals from other axons; in contrast to
Schwann cells, upon losing contact with axons, oligodendrocytes undergo apoptosis
-Most important cells in clearing myelin debris from site of injury are monocyte-derived
macrophages – Schwann cells initiate debris removal first, and then resident macrophages
become activated after injury  proliferate/migrate into injury site and phagocytize debris
-in PNS, a massive recruitment of monocyte-derived macrophages that migrate from blood
vessels and infiltrate vicinity of nerve injury
-when axon is injured, blood-nerve barrier is disrupted along entire length to allow
influx of macrophages to remove myelin
-Inefficient clearance of myelin debris in CNS due to limited access of monocyte derived
macrophages, inefficient microglia phagocytosis, and the formation of astrocyte-derived scar
SEVERELY restricts nerve regeneration
-in CNS, BBB only disrupted at site of injury and not along entire length to limit infiltration of
monocyte-derived macrophages to slow myelin removal
-microglia cells do not have full phagocytotic capabilities of migrating macrophages
-inefficient clearance of myelin debris is major factor in failure of CNS regeneration
-formation of glial (astrocyte-derived)scar fills empty space left by axons
Traumatic degeneration occurs in proximal part of injured nerve – some retrograde
degeneration also occurs in proximal axon and is called traumatic degeneration; usually extends
only for a few intermodal segments, but can be further and actially result in the death of the cell
body
-when motor fiber is cut, muscle innervated by that fiber undergoes atrophy
Retrograde signaling to cell body of injured nerve causes change in gene expression that
initiates reorganization of perinuclear cytoplasm
-axonal injury upregulates a gene called c-jun which is involved in later stages of axon
regeneration
-reorganization of perinuclear cytoplasm happens within few days: cell body and its nucleus
moves periphery  Nissl bodies (granules composed of rough endoplasmic reticulum and
ribosomes) disappear from center of neuron and move to periphery in a process called
chromatolysis (observed 1-2 days after injury)
-changes proportional to amount of axoplasm injured
Regeneration – in PNS, Schwann cells divide and develop cellular bands that bridge a newly
formed scar and direct growth of new nerve process
-division of dedifferentiated schwann cells is 1st step in regeneration of peripheral nerve
-initially, cells arrange themselves in cylinders called endoneurial tubes; removal of myelin and
axon debris from inside tubes causes their collapse
-proliferating schwann cells organize themselves into cellular bands resembling longitudinal
columns called bands of Bungner
-these bands guide growth of new nerve processes (neurites/sprouts) regenerating axons
-a growth cone develops in distal portion of each sprout composed of a filopodium rich in actin
-tips of filopodia establish direction for advancement of growth cone
-growth cone interacts with fibronectin/laminin on external lamina of Schwann cell; if
sprout associates with band of Bungner, it regenerates between layers of external
lamina of Schwann cell; sprout grows at 3mm/day
-after crossing site of injury, the sprouts entering surviving cellular bands in the distal stump;
thee bands guide neurites to their destination/provide environment for growth
-axonal regeneration  Schwann cell redifferentiation and remyelination
-If physical contact is reestablished between motor neuron and muscle, function is
reestablished
-if axon sprouts do not reestablish contact with appropriate schwann cells, they grow in
disorganized manner to result in mass of tangled axonal processes called traumatic neuroma
Clinical Correlation: Reactive Gliosis: Scar Formation in CNS
-CNS injury leads to astrocyte activation and division  hypertrophy, and astrocyte processes
are packed with GFAP intermediate filaments which helps form scar tissue, called reactive
gliosis  permanent scar is most often called a plaque
-microglial activation occurs immediately in any injury to CNS; they migrate toward site of injury
and exhibit phagocytosis to a lesser degree than monocyte-derived macrophages
-gliosis is a prominent feature in diseases like stroke, neurotoxic damage, genetic diseases,
inflammatory demyelination, and MS