Week 3 - Nerve Regeneration and Repair Flashcards
what does post-mortem analysis of Alzheimer’s diseased brain show?
loss of gray matter (and less white matter), especially in temporal lobe near hippocampus (memory formation)
-stains with Tau, unlike normal brain
who gets closed head injuries most, and what do they cause?
soldiers and contact sport players
- damages brain tissue, causing tissue loss
- accompanied by long term changes in mood, depression, and cognitive problems (chain of degeneration)
why is repair of damaged nervous system limited?
neurons become irreparably damaged and are not easily saved or replaced
- immediate cellular environment can become a barrier to repair, especially in CNS
- in PNS, if damaged neurons survive, cellular environment can aid in repair process
what are the 4 things that effective nerve regeneration requires?
- survival of the nerve cell body
- clearance of damaged distal axon, myelin breakdown products, and other tissue debris
- an environment that stimulates new axonal regrowth (creates pathway so axon can regrow and connect)
- guidance cues for axon to find its original cellular target
what is epineurium?
connective tissue sheath that surrounds axons in the peripheral nerve
what does perineurium have?
have ECM PRO that promote axon elongation after injury
-surrounds axons into fascicles
what is Wallerian degeneration?
happens quickly after peripheral nerve injury
- removal of distal axonal fragments and other damaged tissue
- allows surviving/proliferating Schwann cells to align and guide growing axon
- takes many months (grows 1 mm/day, so 1 inch/mo)
between a nerve cut and a nerve crush, which is easier to repair?
compression/crush injuries, b/c there are more axons that are spared after injury
- in nerve cut, all the axons need to regenerate
- still require removal of tissue debris
what is the key to successful regeneration in periphery?
Schwann cells
- normally myelinate peripheral nerve, but can de-differentiate and proliferate, secrete ECM molecules to stimulate axonal sprouting and elongation
- source of growth factors and neurotrophins that promote survival of neuronal cell body
what are bands of Bungner?
remaining “tubes” of ECM from perineurium, w/ Schwann cells that serve as guides for growing axons via guidance cues (along with AChR that remain in muscle)
-allow peripheral axons to reconnect with target muscle
how is repair in CNS compared to PNS?
not very effective b/c, although Wallerian degeneration begins quickly, myelin debris clearance is slow and incomplete
-oligodendrocytes, unlike Schwann counterparts in PNS, don’t help cleanup
what is a glial scar?
generated after damage to CNS (but not PNS) neurons
- inhibits nerve regeneration by forming chemical and physical barrier to repair via CSPGs
- formed, in part, in attempt to limit tissue damage in CNS
what are chondroitin sulfate proteoglycans?
CSPGs (PRO core and GAG side chains)
- make up glial scar
- interfere w/ axonal growth and other cellular repair
- it’s actually the sugar that causes this, so possible to degrade sugar and reveal just inert PRO w/ chondroitinase ABC
are there guidance cues for nerve regeneration in CNS?
no
what are 5 current research strategies to repair SCs?
- biomaterials to provide growth promoting substance for growing axons
- growth factors targets to promote neuronal survival and axonal sprouting
- agents that will change local envirnoment in lesion to promote axonal regrowth
- agents to promote remyelination after injury
- cell replacement therapy to replace neurons or oligodendrocytes
