Cellular Neurobiology of CNS/PNS Diseases (Week 1--Vinters)

Question 1

What part of the brain does not form until after birth?

Answer 1

Cerebellum is one structure where neuronal migration continues through first 16-18 months of life

Question 2

Where do microglial precursors originate from?

Answer 2

Bone marrow

Note: microglial precursors colonize CNS during first trimester of pregnancy, leading to well-established microglial population by second trimester

Question 3

Primary vs. secondary demyelination

Answer 3

Primary demyelination: primary degeneration of a myelin sheath when axon is intact/preserved; not related to specific tracts; key event in demyelinating diseases like MS

Secondary demyelination: degeneration of myelin sheath that results from degeneration of the ensheathed axon; affects specific tracts; mechanism is Wallerian degeneration; occurs in many diseases (infarct, etc)

Question 4

Central chromatolysis

Answer 4

Occurs proximal to cut in axon, at the neuronal cell body

Neuron body swells and nucleus and Nissl are pushed to periphery of cell body

Loss of normal basophilic appearance of cell body

May be reversible or may progress to death of neuronal cell body

Question 5

Wallerian degeneration

Answer 5

“axonal neuropathy”

Breakdown of axon distal to cut

Question 6

Retrograde degeneration

Answer 6

“distal axonopathy”

Progressive injury from distal to proximal axon

Can cause neuronal cell body to atrophy

Question 7

Trans-synaptic degeneration (TSD)

Answer 7

Neuron or group of neurons (entire nucleus) undergoes atrophy when major synaptic input is lost (due to infarct, traumatic injury, etc)

Slow process, progresses over months to years

Question 8

Four ways that neuronal cell bodies may undergo irreversible injury

Answer 8

1) Anoxic-ischemic change: inadequate O2/blood delivery to the high energy-dependent neuron
2) Excitotoxicity: neurons overstimulated because of excessive glutamate stimulation
3) Programmed cell death: poorly understood mechanism; probably significant in neurodegenerative diseases
4) Metabolic storage diseases: cytoplasm becomes distended with excessive potentially toxic metabolites and lysosomal products (Tay-Sachs disease)

Question 9

Four types of glia in CNS

Answer 9

1) Astrocytes: most abundant cell type of brain, supporting cells in CNS, regulate fluid and ion balance (mop up NT), cerebral microvascular endothelium (maintain BBB), regulate glutamate levels
2) Oligodendrocytes: small, regular, round cells with short processes (fried egg appearance) that provide myelin sheaths for several CNS axons
3) Ependyma: line ventricular system, have limited repertoire of responses to injury
4) Microglia: derived from bone marrow, are scavenger cells that proliferate in response to CNS injury

Question 10

Cortical ribbon

Answer 10

Cerebral cortex on the outside of the brain

Gray matter

Note: there should always be a clear line between cortex and white matter

Question 11

Contents of posterior fossa

Answer 11

Brainstem (midbrain, pons, medulla oblongata)

Cerebellum

Question 12

Neuropil

Answer 12

“extracellular” fibers of astrocytes, neurons, etc (unmyelinated axons, dendrites, glial cell processes)

Low number of cell bodies in neuropil area

Amorphous

Eosinophilic

Question 13

Nissl substance

Answer 13

Rough ER (protein synthesis factory!)

Question 14

What can happen if infarct kills cell bodies in the brain?

Answer 14

Corticospinal tracts (really long!) can degenerate