Nerve Regeneration and Repair

Question 1

Chronic traumatic encephalopathy

Answer 1

• Caused by repeated blows to the head
• Brain shows increased staining for Tau protein which is typically associated with Alzheimer’s
• Can be observed in very young patients

Question 2

Requirements of effective nervous system repair

Answer 2

• Survival of the nerve cell body
• Clearance of the damaged distal axon, myelin breakdown products, and other tissue debris
• Environment that stimulates new axonal regrowth
• Guidance cues for the axon to find its original cellular target
• Only occurs in PNS

Question 3

Myelinating cells in the PNS

Answer 3

• Schwann cells
• Promote nerve regeneration after injury
• Will de-differentiate and proliferate, secreting extracellular matrix molecules that stimulate axonal sprouting and elongation
• Source of growth factors and neurotrophins

Question 4

Epineurium

Answer 4

-Tough connective tissue sheath surrounding the peripheral nerve

Question 5

Perineurium

Answer 5

• Protective sheath

- Composed of extracellular matrix proteins that can promote axon elongation after injury

Question 6

Wallerian degeneration in PNS

Answer 6

• Key event in peripheral nerve repair
• Removal of distal axonal fragments and other damaged tissue
• Allows for schwann cells to align and guide the growing axon

Question 7

Guidance cues for reinnervation

Answer 7

• Bands of bungner–formed by ECM

- ACh receptors that remain in muscle allow for precise reinnervation

Question 8

CNS nerve injury

Answer 8

-Not as effective as in PNS

Question 9

Wallerian degeneration in CNS

Answer 9

• Axonal segments proximal and distal to injury exhibit short-distance acute axon degeneration (mediated by extracellular Ca2+ influx and activation of the intracellular Ca2+ dependent protease calpain.)
• Axonal retraction and formation of axonal bulbs at injury site
• 72 h after injury rapid fragmentation and cytoskeletal breakdown occurs
• Followed by increased glial influx to clear axonal remnants and to possibly promote regenerative attempts
• Wallerian degeneration is incomplete in the CNS and thus inhibits regeneration–oligodendrocytes don’t do a good job clearing debri

Question 10

Glial scar

Answer 10

• Created after damage to CNS neurons
• Produced by astrocytes
• Inhibits nerve regeneration–chemical and physical barrier
• Formed to limit tissue damage
• Chondroitin sulfate proteoglycans CSPGs

Question 11

Failure of CNS neurons to regenerate

Answer 11

• CSPGs in glial scar
• Myelin debris not effectively cleared from lesion site
• Expression of TNFs, FGFs, Lingo, Nogo and its receptors, interleukins, interferons

Question 12

Peripheral nerve grafts

Answer 12

• Can be used in PNS or CNS to promote repair
• Provides growth factors and permissive substrate
• Physical therapy important after–neurotrophins

Question 13

Chondroitinase ABC

Answer 13

• Enzyme that can remove sugar side chains from inhibitory proteoglycans that are expressed in the glial scar
• Creates a permissive environment

Question 14

Cell replacement therapies

Answer 14

• Stem cells–replace neurons lost

- Olfactory bulb and hippocampus are the most apt from the brain to work