nerve regeneration and repair Flashcards
what can cause damage to nervous system occur:
- acute injury: tbi, spinal cord injury, strokes, limb damage
- degenerative diseases with loss of neurons; alzheimer’s parkinson’s, ALS
- loss of myelin: MS
What part of the brain is really deteriorated in alzheimer’s patients?
grey matter esp. in the temporal lobe in the area of the hippocampus
what is tau?
a protein associated with neuronal damage seen in alzheimer’s
what accompanies brain tissue damage in tbi of football players and soldiers?
changes in mood, depression, and cognitive problems
what is required for nerve regeneration>
- survival of the nerve cell body
- clearance of the damaged distal axon, myelin breakdown products, and other tissue debris
- an environment that stimulates new axonal
- guidance cues for the axon to find its original cellular target
what is the critical step for nerve repair in the CNS and PNS?
wallerian degereneratlon
what is perineurium composed of?
ECM proteins that can promote axon elongation after injury
if any nerve regrowth does occur how long does it take?
it can take weeks ,months, a year
what is wallerian degeneration?
removal of damaged axons, damaged tissue and myelin debris
what is the role of schwann cells in the regeneration of axons?
schwann cells release trophic agents to align and guide growing axon.
when does wallerian degeneration start?
it is underway within 1 week of injury ( quickly w/ in 5-30 minutes of the injury)
a nerve cut is harder to repair than a nerve __________
a nerve crush ( compression)
in a nerve crush what happens to the axons?
some axons remain , density just decreases. the surviving ones can make new connections.
but you must get rid of the debris before axons can regrow in both crush and nerve cut
what is the key to successful regeneration in the periphery?
schwann cells : they normally myelinate peripheral nerve, but in this case they will differentiate and proliferate secrete ECM proteins that stimulate axonal sprouting and elongation
they area also a source of neurotrophins
what is the role of the bands of bungner?
they are the remaining tubes of ECM that act as guidance cues
how do PNS nerves that regenerate know where to reconnect with muscle?
the Ach receptors remain where axons terminates and therefore provide guidance cues for regenerating axon to find where previous axons were.
the reinnervation of muscles following peripheral motor nerve damage is ________
precise
compared to the PNS the repair in the CNS is ?
not very effective
most studies of CNS repair are centered around trying to restore _______ ________ after ______ ______ _______
restore motor fnc after spinal cord injury
even though many there is often prolonged survival of neuronal cell body in the CNS why is it that effective regeneration is not seen?
because the other 3 requirements are exhibited ( clearance of damaged distal axon, environ which stimulates axonal regrowth, guidance cues for the axon to find it’s original cell target)
what is the reason why wallerian degeneratioin is inefficient in the CNS?
because when myelin breaks down some of the products are inhibitory to axonal regeneration: a GLIAL SCAR is formed in an attempt to limit tissue damage in the CNS this forms a physical barrier to repair .
what does a glial scar produce?
chondrotin sulfate proteoglycans which forms a physical barrier to regeneration and remyelination
in what disease processes are chondrotin sulfate proteoglycans seen?
multiple sclerosis, Alzheimer’s etc.
how does a graft help with nerve regeneration?
provides a source of growth factors to stimulate axonal regeneration and neuronal survival as well as a permissive on which axons can easily grow.
how does chondrotinase treatment help nerve regeneration?
it removes the sugars from the chondrotin sulfate proteoglycans essentially removing the barrier which the sugar cause , this creating a permissive environment where axons can regenerate and oligodentrdrocyte progenitor cells can move in and remyelinate axons.
where are the only neurons that can be replaced if a neuron is lost?
the adult brain olfactory bulb and the hippocampus
what is a major problem for stem cells within the CNS?
guidance cues and pathways ( i.e. lack thereof)
neural stem cells are?
committed but multipotenet
what type of stem cells are pluripotent and what issues do these cells pose?
embryonic stem cells ( sometimes they don’t differentiate, and they are tumorgenic)
adult stem cells are
multipotent
to successfully restore function to a stem cell what must be achieved?
- cell must differentiate into the appropriate kind of neuron
- make connections w/ the appropriate target cells
- form working synapses
how does differentiation of stem cells into oligodentrocytes help regeneration?
it enhances the remyelination of spared axons near the lesion which enhances the ability of axons to transmit nerve impulses
what is the best option for repair?
combination of therapies to enhance tissue recovery and restore fnc
how can physical therapy help with regeneration/repair?
can stimulate the endogenous production of neurotrophins that promote repair
