Neuropathology DeMasters/Ojemann

Question 1

1. Identify the basic components of the neuronal cytoskeleton and describe how alterations of some of these components are associated with neurodegenerative diseases.
2. Identify neurons and all type of glial cells, and describe their normal functions and reactions to injury.
3. Discuss the significance of the rough endoplasmic reticulum (RER aka Nissl substance) and how it reacts to axotomy.
4. Discuss the uses of silver stains in the histological study of the CNS.
5. Recognize that GFAP is a key protein of astrocytes.
6. Describe the role of microglia in CNS inflammation and repair.
7. Describe the structure of sarcolemma and key intracellular, transmembrane, and extracellular proteins associated with it, and how they are involved in the pathogenesis of muscular dystrophies.
8. Describe how type I and type II fibers are distributed in normal muscle and in the denervation atrophy.
9. Compare and contrast central and peripheral myelin.
10. Describe the pathogenesis and pathological process of Wallerian degeneration and segmental demyelination and discuss which of these represents a faster recovery.
11. Describe how myelin is formed and what cells make myelin in the CNS and PNS.

Answer 1

x

Question 2

What characterizes chromatolysis, histologically? What is the “definition”?

Answer 2

Chromatolysis—an attempt by the cell body of the neuron
to “regroup” and regrow/repair a damaged axon—or die
in the process!

In cross-section, will see a swollen cell body without the characteristic Nissl substance. (Big, pink, and empty)

Question 3

What are the histological manifestations of parkinsons? In what region of the brain are they seen?

Answer 3

Cytoplasmic inclusions in the neurons of the substantia nigra. Termed “Lewy bodies.”

Question 4

What two histological features are visible in Alzheimer disease? Which is intracellular? What is thie molecular basis of each, and how are they visualized?

Answer 4

Neurofibrillary tangle - intracellular, silver stain. Phosphorylated Tau protein leads to disruptions in axonal transport and cell death.

Beta-amyloid - extracellular, visualized with HE stain,

Question 5

What is Wallerian degeneration?

Answer 5

Necrosis of the axon distal to the cell body.

Question 6

How can astrocytes be visuallized, histologically?

Answer 6

Staining the GFAP protein (immunostaining)

Question 7

What are the two MAIN functions of astrocytes, and what is the response to injury? How does this compare to the other tissues in the body.

Answer 7

1. K balance in the neuropil
2. Response to injury - no fibroblasts in the CNS. Instead of laying down collagen, the astrocytes extend more processes, but these cannot fill the scar. Leaves “hollowed-out” areas of injury. (Chronic gliosis - cytoplasmic expansion and extension of cell processes).

Question 8

Ependymal cells line the ____.

Answer 8

ventricles. have cilia

Question 9

What do microglial cells do?

Answer 9

Microglial cells are sentinels within the brain, monitoring the immunologic milieu and awaiting need for response to tissue injury. Microglia cells proliferate and respond to injury and are replenished by blood monocytes

Question 10

What are characteristics of Type I muscle?

Answer 10

Type I = Red (dark meat in birds) = Slow Twitch
Oxidative enzymes
More mitochondria
More myoglobin
Slower relaxation/contraction

Question 11

What are characteristics of Type II muscle?

Answer 11

Type II = White = Fast twitch
Gylcolytic enzymes
more fatiguable

Question 12

What determines muscle types? What happens when a given muscle is denervated?

Answer 12

The innervation determines the muscle fiber types. When you denervate a muscle, you switch from a mixed distribution of Type I/II to discrete bundles of Type I/II.

Question 13

What differentiates myopathy from denervation?

Answer 13

Myopathy: elevated CK, proximal weakness
Denervation: level CK, distal weakness

Question 14

On an EMG, how would axonal loss be differentiated from demyelination?

Answer 14

Demyelination: slowed conduction speed

Axonal loss: lower amplitude

Question 15

10. Describe the pathogenesis and pathological process of Wallerian degeneration and segmental demyelination and discuss which of these represents a faster recovery.

Answer 15

Wallerian degeneration - Axon chopped (trauma, infarction, diabetes) Takes months to recover, (2-3mm/day at best)
Distal axonopathy - No “packages from the mothership” (often toxin mediated)
Segmental degeneration - eg MS (can see increases in conduction due to Na channel insertion)

Question 16

Under what circumstances does the “onion bulb” form?

Answer 16

In response to segmental demyelination (eg Charcot Marie Tooth)