Nerves can sometimes regenerate in the ___
Nerves can almost never regenerate in the ___
Effective nerve regeneration requires: (4)
1. survival of the nerve cell body (damage to axon only) 2. clearance of the damaged distal axon, myelin breakdown products, and other debris 3. a supportive environment that stimulates new axonal regrowth (limited inflammation) 4. guidance cues for the axon to find its original cellular target
after injury CNS Wallerian degeneration is ___ and ___
slow and incomplete
what is one reason why the CNS is a hostile environment for tissue regeneration? *
1. oligodendrocytes don't help clean up debris so myelin persists in the CNS
2. CNS neurons result in a glial scar (purpose was to limit tissue damage -- but now serve as a barrier)
in PNS injury Denervated myelinating Schwann cells release their myelin and ___
proliferate, produce trophic factors, and phagocytose debris (~24 hours)
After a nerve injury in the CNS and PNS, Wallerian degeneration occurs where the axon that is cut off is ___ and ____
degenerated and its myelin sheath degraded
After nerve injury ___ and ___ are recruited work to clear away the debris.
schwann cells and macrophages
after pns injury The macrophages produce factors that facilitate ___ and ___
Schwann cell migration & axon regeneration
Injured axons form a growth cone and regenerate along the ___ formed by Schwann cells
bands of Bungner
bands of Bungner guide the___ to their targets
Schwann cells that are chronically denervated for a few months are less supportive of regrowth and more likely to ____
If the axon can traverse the injury site, it may reconnect successfully. this typically takses
months to years
compared to the original, the regenerated axon will have
thinner myelin and shorter nodal length
why are come compression injuries easier to repair?
some axons may be spared - easier to repair.
____ of muscles following peripheral motor nerve damage is precise - almost exactly the same as before injury
what does the CNS lack that may it ineffective at repair? (3)
1. clearence of debris
2. a supportive environment
3. guidance cues
- acute axon degeneration is mediated by __ and ___
Ca influx and activation of calpain
For___ hours after injury, the distal (disconnected) axon remains stable.
Full fragmentation and breakdown of the distal axon occurs ~___ hours after injury,
after full fragmentation and breakdown of the distal axon, ___ occurs
increased glial support (astrocytes and macrophages) to clear debris
in PNS, Schwann cells shed myelin and ___.
in CNS, oligodendrocytes shed myelin and ____.
don’t usually proliferate
Main culprit of the glial scar =
CSPG, chondroitin sulfate proteoglycans
CSPG, chondroitin sulfate proteoglycans are produced by
astrocytes in response to injury, inflammation, or disease
what are 6 Strategies to promote repair of the damaged nervous system:
1. biomaterials or peripheral nerve grafts
2. growth factors
3. agents to change local environement
4. cell replacement therapy to replace neurons or olgiodendrocytes
5. physical therapy
how can Chondroitinase ABC help change local environements?
its an enzyme that can remove sugar side chains from
inhibitory proteoglycans of the glial scar
Biomaterials or Peripheral Nerve Grafts could be used to provide a ____
a growth-promoting substrate
Growth factors could be used to promote___ and ___
neuronal survival and axonal sprouting
The perineurium is composed of extracellular matrix proteins that can promote ____
axon elongation after injury.
The key to successful regeneration in the periphery is the ____
regneerating axons can reconnect with target tissues because of guidance cues provided by ___ and ____
bunger and ach receoptors
why is the concept important that "if the neuron is lost it cant be replaced"
without the neuron, you cannot get repair (need surviving cell body)
what are some stem cell soruces?
in addition to replacing cells that were lost, what could stem cells also be useful for?
Differentiation of stem cells to oligodendrocyte progenitor cells prior to transplantation enhances the remyelination of spared axons near the lesion
physcial therapy can stimulate the endongeous poduction of ___ that promote repair