Mechanisms of Neurodegen/ Regen

Question 1

What are the four things that are required to get nerve regeneration?

Answer 1

1. Survival of the cell body
2. Removal of the damaged distal axon, myelin breakdown products and other debris
3. An environment that stimulates new axonal regrowth (neutrophins)
4. Guidance cues that tell the axons where to grow and synapse

Question 2

What is the difference between the epineurium and the perineurium of a peripheral nerve? Which of these is capable of axon elongation?

Answer 2

Epineurium: connective tissue that pulls all the axon bundles within the nerve together; outermost
Perineurium: sheath produced by Schwann cells that surrounds the groups of axons; the perineurium is capable of axon elongation

Question 3

What is Wallerian degeneration? What cells are responsible for Wallerian degeneration?

Answer 3

Process of removing distal axonal fragments and other damaged tissue. Schwann cells and macrophages are responsible (Schwann cells release cytokines that recruit more macrophages)

Question 4

The remyelination following Wallerian degeneration is accomplished by which cell? Is the new myelin thicker or thinner than the original?

Answer 4

Schwann cells; thinner

Question 5

Which cells secrete extracellular matrix and neutrophins that stimulate axonal growth and guide the axon to the correct target in PNS?

Answer 5

Schwann cells

Question 6

How does a regenerated peripheral nerve know where to go on the target muscle (what are the guidance cues)?

Answer 6

The Schwann cells produce extracellular matrix within a tube known as Bands of Bunger that guide the axon. The ACh receptors on the muscle also remain intact and tell the growing axons where the neuromuscular junction should be

Question 7

CNS or PNS repair is more effective?

Answer 7

PNS

Question 8

Both CNS and PNS repair require four steps to get effective regeneration. What steps aren’t present in CNS repair?

Answer 8

The tissue debris isn’t completely cleared, nor is the environment conducive to growth. Also, there aren’t any guidance cues

Question 9

Although Wallerian degeneration occurs during CNS repair, there is not effective clearance of tissue debris. What remains even after Wallerian degeneration?

Answer 9

Myelin- as long as the myelin is present regeneration can’t occur

Question 10

What is a glial scar? What cells are responsible for the formation of a glial scar? Is a glial scar conducive to nerve regeneration?

Answer 10

A physical/chemical barrier that is made to prevent further damage to the CNS. The glial scar is made by astrocytes and other cells that make chondroitin sulfacte prostaglandins. A glial scar is not conducive to nerve regeneration as it provides a physical barrier

Question 11

How are oligodendrocytes different from Schwann cells in nerve repair?

Answer 11

Oligodendrocytes release inhibitors of axonal growth

Schwann cells release neutrophins that support growth and guide the axon

Question 12

There are numerous strategies to get CNS repair. What are some of these strategies?

Answer 12

Try and remove the glial scar by chrondroitinase ABC
Cell replacement therapy- replace neurons/oligodendrocytes by using a PNS graft (provides a more permissive environment with guidance cues) or by using stem cells
Functional therapy- physical/cognitive therapy after injury in attempt to enhance neuroplasticity; physical therapy may stimulate endogenous production of neutrophins