: large spherical nucleus and prominent nucleolus both centrally located
abundant RER visible as Nissl substance
accumulate lipofuscin (yellowish, brown) with age Þ accumulation of membranous material due to lipid peroxidation (normal process, not pathological)
Special Considerations
: cannot reproduce (post-mitotic); function depends on membrane excitability of the dendritic tree; function depends on integrity of glial cells; relatively isolated by blood-brain barrier
Pathology of the Neuron
Ischemic (anoxic) neuronal damage – the "red neuron"
most vulnerable area to ischemia Þ CA1 region of hippocampus (Sommer sector region)
CA3-4 region is enclosed by dentate gyrus (dark purple)
eosinophilic or red appearance of cytoplasm when ischemic (acutely dead, 1-2 days) Þ dispersed Nissl substance, shrunken nucleus, disintegrated nucleolus
ischemia (lack of blood flow) to the brain is far worse than anoxia (blood flow with low oxygen)!
other vulnerable areas Þ Cerebral purkinjie cells, laminar cortex layers 3-6, areas between vascular territories (arterial border zones)
Intermittent repetitive neuronal injury (occurs during epilepsy)
Þ (nesotemporal sclerosis) hippocampus is small and shrunken on affected side
cells replaced by glial tissue
excessive neurotransmitters damaging the neurons
extensive loss of pyramidal cells from CA1, somewhat less extensive loss of neurons from CA3-4, some loss of dentate granule cells accompanied by reactive astrocytosis (Ammon’s horn sclerosis)
results from the seizure activity itself and is not dependent on systemic factors (apnea, etc)
Chronically stressed neurons
– Alzheimer’s neurofibrillary degeneration
neurofibrillar tangles – thickening and tortuosity of fibrils within the neuronal cytoplasm; composed of abnormally phosphorylated neurofilaments and hyperphosphorylated microtubule associated (tau) proteins
occurs in aging and Alzheimer’s disease (Alzheimer’s associated with greater quantity, not quality)
secondary to trauma, tumors or cerebral infarction (i.e., corticospinal tract degeneration after infarction of motor cortex)
takes months for myelin to disappear – Markee stain picks up degenerated myelin fragments
axonal swellings (intracellular accumulation) so not resorbed and sticks around long after the insult
Proximal to the cut
Þ primary axonal damage (posterior column damage)
usually results from infarction or local forces (i.e., compression, radiation injury)
Þ axonal swelling
central chromatolysis or axonal reaction (perikaryal reaction to axonal injury)
Þ cell body fills up with organelles, nissl substance etc, so nucleus is pushed off to the side (becomes eccentric)
Trans-synaptic (transneuronal) degeneration
Þ neuronal degeneration secondary to loss of afferent input
a good example is the visual system
Þ lateral geniculate nucleus (2,3,5 or 1,4,6 will be damaged)
results from loss of neutrophic support to the innervating neuron
The Astrocyte
Normal Function
: metabolize NTs that may become toxic, maintain ion (K+) homeostasis, respond to injury by producing glial filaments, developmental scaffolds for migrating neuroblasts, aid capillaries in forming blood brain barrier
GFAP (glial fibrillary acidic protein) – produced by astrocytes in increased amounts when brain is damage
Divisions
: fibrous (in white matter) and protoplasmic (in gray matter) subtypes also radial or non-radial astrocytes
Radial astrocytes: used in cerebellum to help neurons in outer granular layer migrate down into inner granular layer
Pathology of the Astrocyte
Astrocytic Scar (Reactive astrocytosis) Þ Ý production of GFAP in response to injury Þ may impede axonal regeneration
Alzheimer type II astrocytosis (nothing to do with Alzheimer’s disease) Þ reaction to Ý amounts of ammonia (hepatic encephalopathy) Þ produce Ý amounts of enzymes that break down the ammonia at the expense of ß structural protein synthesis Þ enlarged hypochromatic nuclei and few intermediate filaments
Alzheimer type I astrocytosis Þ very uncommon (seen in Wilson’s disease) Þ enlarged, multinucleated nuclei
Astrocyte Inclusions
Þ Rosenthal fiber (his personal favorite) Þ eosinophilic (ruby red) long rod fibers that accumulate in cytoplasm of astrocytes; pathologic for chronic cystic lesions of astrocytes; diagnostic for pilocytic astrocytoma
Alexander’s disease
Þ results in huge numbers of rosenthal fibers Þ no known metabolic defect in this disease
Corpora amylacea
Þ big spherical purple cells (basophilic) in terminal processes of astrocytesÞ accumulate with age, normal process (non-specific accumulation of sulphated glycolipids)
Oligodendroglia
Normal Structure/Function
: small cell; small round dark nucleus with dense clumps of chromatin, sometimes with halo; look like fried egg; cytoplasm does not contain GFAP; found in white matter; primary function = myelination
extends processes to myelinate multiple axons (3-8); Schwann cells extends one process to only one axon
tendency to cluster in the white matter and around neuronal perikarya and blood vessels (referred to as satellites or perineuronal satellite cells) – unknown function in these locations
Pathology of the Oligodendroglial Cell
delicate cells vulnerable to immunologic injury, responds to injury by dying (results in myelin loss); cell type most vulnerable to ischemia/anoxia in the white matter
Multiple Sclerosis
Þ demyelinating disease Þ oligodendrocytes drop out
possibility of regeneration
Þ may be capable of proliferation and (limited) remyelination within the CNS
inclusions – JC virus
Þ PML
Ependyma
Normal Structure/Function
: ciliated astrocyte-like cells that line the ventricular system; do not form a barrier to fluid
Tanycytes
Þ subtype, very elongate processes that terminate on capillaries; Only found in floor of 3rd ventricle; May mediate communication between ventricular system and the blood Þ "ventricular route hypothesis": tenycytes pick up active compounds secreted into the ventricular system and deliver them to their target circulations
Pathology of Ependyma
respond to injury by sloughing off and cannot reproduce themselves Þ result in subependymal nodules
Granular ependymitis
Þ gives rise to granular appearance Þ classic case occurs in neurosyphilis
opaque, yellow substance lining the ventricles
Þ halts flow resulting in hydrocephalus
Choroid Plexus
Normal Structure/Function
: arise from invagination of ependyma into the ventricular cavities by the blood vessels of the pia mater; choroidal epithelium is composed of a single row of epithelial cells, thrown into villi around a core of blood vessels; specialized for fluid transfer Þ one way flow
tight junction formation with CSF production (500 cc per day); not only source of CSF production but majority
Pathology of the Choroid Plexus
99.9% of hydrocephalus is due to obstruction; but theoretically, can result from overproduction from choroid plexus
favored site of bacterial entry into the CNS
Microglia
Normal Structure/Function
: monocyte, macrophage type of cell derived from bone marrow; functions include phagocytosis, cytokine secretion, and antigen presentation; they are the brain’s resident macrophages
rod shape appearance when activated
Pathology of Microglia
in necrotic/demyelinating processes, microglia become macrophages and phagocytize myelin and cellular debrise; if blood-brain barrier is broken down, the macrophage population is derived from circulating monocytes
when activated in viral infection Þ formation of microglial nodules (they cluster together)
may target neurons for destruction when activated Þ neuronal phagia (occurs during viral infection)
HIV encephalitis
Þ microglial cell is the primary cell type that encases the virus in the brain Þ infected microglial cells secrete toxins, cytokines, etc
may play a critical role in the pathogenesis of Alzheimer dementia (intimately associated with the senile plaques)
Capillary Endothelial Cells
Normal Structure/Function
: facilitate formation of the blood-brain barrier (tight junction formation in endothelium)
Pathology of the Capillary Endothelial Cell
Vasogenic edema: capillaries leak without BBB Þ cellular edema (vasogenic edema) Þ accumulates in white matter
associated with brain tumors, abscesses, hemorrhages, infarcts, contusions, and meningitis and is responsible for the characteristic increases in CSF protein seen in these disorders
can displace the hemispheres and when severe, is responsible for various types of cerebral herniation
appeared green in example presented in class due to the patient having jaundice
Herniation
– mass effect in brain Þ responds by shifting Þ many types (uncal, trans-tentorial, tonsillary, subfalcium)
Microscopic Vascular Anatomy
each artery that penetrates the CNS is surrounded by a perivascular space lined by 2 basal laminae which eventually fuse as the vessel becomes a capillary
The perivascular space is entirely Subpial space, not a subarachnoid space