CENTRAL NERVOUS SYSTEMCENTRAL NERVOUS SYSTEM• neurocytology

a) cells include neurons, glia, meninges and cells composing vasculature• NEURONSNEURONS:

a) composed as either i) aggregates - such as nuclei or ganglia

ii) elongated columns - such as in spinal column or iii) layers - of cerebral cortex

b) vary in structure, size and cytoplasmic composition

c) features consistent to neurons are: i) microtubules

ii) neurofilamentsiii) Golgi apparatus and iv) rER

d) Mature neurons do not dividei) loss of neurons with ageii) neurons of CNS do not

regenerate over long distancesiii) infarcts that transect internal

capsule permanent motor deficits

e) CNS neurons do not remyelinatei) MS causes permanent deficits

• Anatomya) centrally, round nucleus contains prominent nucleolusb) cytoplasm is abundant

i) ribosome-studded ER forms prominent basophilic granules

known as Nissl bodiesii) some neurons, of the

substantia nigra and locus ceruleus contain pigment termed neuromelanin

Normal Neuron

Pigmented Neuron

neuromelaninneuromelanin

• Neurons react to injury in several ways:a) chromatolysis

i) injured neurons swell, cytoplasm expands and Nissl substances

disperse near the plasma membrane

ii) nucleus becomes eccentriciii) these processed (i and ii) are known as chromatolysis and is

common response to injury- may be reversible or progress to

irreversible damage

ChromatolysisChromatolysis1.Swollen2.Nissl margination3.Pale cytoplasm4.Eccentric nucleus

b) atrophyi) loss of neurons in brain – aging

processii) may be global or regionaliii) single neurons may shrivel and

become hyperchromatic (e.g., “Creutzfelt-Jacob disease”)

c) neuronophagia (phagocytic response)i) injuries that kill neurons create

debris and elicit phagocytosis by brain macrophages or microglial cells

Atrophy (Creutzfeld-Jacob disease)1.Injured neurons shrivel and2.Are hyperchromatic

Spongiform changes

d) intraneuronal inclusionsi) diverse neuronal and

cytoplasmic inclusions affect neurons (e.g., viral encephalitides and degenerative diseases)

- cytomegalovirus induces inclusions (both nucleus

and cytoplasm) (intranuclear) with prominent clear “halos”

- rabies encephalitis induce cytoplasmic “Negri

body”, which resemble RBC

cytomegalovirus

Negri Negri BodyBody

- Lewy bodies of Parkinsons disease

- Cowdry bodies as seen in herpetic infections

- Neurofibrillary tangles (intracytoplasmic)

AstrocytesAstrocytes

• Support neurons and promote repaira) star shaped glial cells

i) outnumber neurons throughout CNS

b) 2 prominent types:i) fibrillary astrocytes (white

matter)ii) protoplasmic astrocytes (grey

matter)iii) Glial Fibrillary Acidic Protein

(GFAP) or silver impregnation stain demonstrate processes

extending in all directions from cell body, some terminating as foot process on blood vessels

iv) proliferate locally in response to injury (trauma, abscess,

tumors, infarcts and hemorrhages). This process is referred to as

“astrocytosis” or “gliosis”

- most important histopathologic indicator of CNS injury, regardless of etiology

- evolves over hours to days and presence commensurate with severity of injury.

- result in “glial scar”

- Astrocytes undergo hypertrophy (e.g., cell swelling – edema)

and hyperplasia - cytoplasm expands to bright pink

(gemistocytic Astrocytes)- long standing gliosis associated

with Rosenthal fibers (bright, thick, elongated eosinophilic structures). Also associated with cerebellar pilocytic astrocytoma and reactive brain structures adjacent to craniopharyngioma

Astrocyte proliferation

GFAPGFAPSilver carbonateSilver carbonate

v) astrocytes may undergo neoplastic transformation resulting in most common primary brain tumor named “glioma” or “astrocytoma”

c) corpora amylaceai) 5-50 m basophils and

amorphous structures which accumulate with normal aging in the subpial and subependymal regions

- extracellular that evolve within processes of Astrocytes

ii) represent degenerative change in astrocyte

iii) composed of polyglucosan

Corpora amylaciaCorpora amylacia

d) Alzheimer type II Astrocytesi) unrelated to Alzheimer diseaseii) occurs most often in patients

with long standing:- hyperammonia (due to liver

disease) - Wilsons disease

- hereditary metabolic diseases of urea cycle

ii) GliaGlia- AstrocytesAstrocytes: found

throughout CNS (grey and white

matter).- act as BBB- metabolic buffers- repair and scar formation

iii) Oligodendrocytes- myelination ( on multiple

axons)- damage mediated via

acquired demyelination diseases (e.g., MS)

- may harbor viral inclusions iv) Ependymal cellsEpendymal cells

- line ventricular system

• Regulate fluid transport (CSF)a) single layer of cells line the four ventricular chambers, aquaduct

of Sylvius, central canal of spinal cord and filum termianle.

b) during gestation, some viral infectious target ependymal cells which

may result in congenital hydrocephalus

c) ependymomasi) usually arise within ventricles but may also appear in spinal cord

and filum terminale

Ependyma

v) MicrogliaMicroglia- primary function to serve as

fixed macrophages- proliferate with injury and develop elongated

nuclei (“rod cells”)• Reactions of neurons to injuryReactions of neurons to injury

a) several forms: degeneration and cell death (necrosis and apoptosis)

i) acute neuronal injury (redred neuron)

- result from acute CNS hypoxia/ischemia (12-

24 hrs)- or any insult which results in cellular death

MicrogliaMicroglia

- cell body atrophy- pyknosis of nucleus- loss of Nissl substance- intense eosinophilia of

cytoplasmii) Subacute and Chronic neuronal

injury (degeneration)- result of a progressive

disease- seen early as reactive gliosis (i.e., best early indicator) (early cell loss often difficult

to determine!!)

iii) Axonal reaction- refers to axonal

regeneration- associated with protein synthesis- extensively studied in motor neurons of experimental

animals