Injury and Repair of the Nervous system Flashcards
what happens after nerve injury
- After revascularixation a composite tissue allograft is viable but it is not functional
- The axons of the recipient have to regrow and replace the axons of the donor to reinnervate the muscles and the sensory end organs within the graft
- The donor nerves severe as temporary scaffold for the axons to grow into
describe what happens with axonal damaged
- initially the damage is localised and then it may spread to the synaptic boutons and towards the cell body as parts of the nerve is degenerated
what does anterograde degeneration mean
this involves the distal parts of the axon and occurs rapidly
- segment of the axon swell and break apart over 2-3 days
what does retrograde degeneration mean
- involves changes to the proximal part of the axon from the site of damage to the soma over 2-3 days
what are the ways in which nerve segregation spreads
retorgrade degeneration
anterograde degeneration
what are the challenges of nerve repair
- Nerve repair is not always successful
- Nerve damage may spread
- The success of repair depends on the severity of the injury (primary and secondary)
when is repair successful and when is it not successful
- Repair may happen when damage is not localised but attempts might not be successful
- Repair always happens when damage is localised
what does the success of nerve repair depend on
- Severity of initial injury
- Location of injury
- the extent of Secondary damage
what is the spread of injury due to
trans neuronal degeneration
what do severed nerves do
Leave a lot of debris
Stop transmission
what is a primary injury
where nerve was cut but this is
never localised and it spreads (causing secondary
damage) by:
Anterograde degeneration/ Wallerian degeneration
Retrograde degeneration/ axonal die-back
what is primary damaged
- what has been damaged
- how much has been damaged
what are the types of nerve injury
neurapraxia - mild
axonotemesis - moderate
neurotmetsis- severe
describe neurapraxia
- this is loss of motor and sensory function due to blockage of nerve conduction
- 1st degree damage
- myelin is not in tact
- it is reversible
describe Axonotmesis
- a disruption of axons, resulting from severe crush or contusion
- 2nd degree damage
- myelin is not intact
- axon is not intact
- there is wallerain degeneration
- it is reversible
describe Neurotmesis
- Both the axons and nerve sheath are damaged
- 3rd degree
- myelin is not intact
- axon is not intact
- epineurium is not intact
- there is wallerain degeneration
- it is irreversible
what happens when there is axon damage
- Burst of action potentials stimulate the dorsal root ganglion of axon
- This disrupts the retrograde transport flow of trophic support
- Causes neurotrophic factors from innervated cells to be released and taken up by nerve terminals
- Injury signals taken up by the cell body and cause:
- Cells in dorsal root ganglion change phenotype from a transition
state to a growth state by upregulating axonal growth proteins
what do the neurotrophic factors do
- released by innervated cells
- taken up by the nerve terminals
- transported retrogradely to the neuronal cell body to promote neuronal growth and survival
what are the examples of neurotrophic factors
- NGF: Nerve Growth Factor
- BDNF: Brain-Derived Neurotrophic Factor
- GDNF: Glial cell-Derived Neurotrophic Factor
describe what happens with axon damage when there is severe damage
SEVERE injuries:
Wallerian degeneration may have to occur completely before
regeneration can start. This often leads to complete loss of
connection to spinal cord, in which regeneration cannot occur.
how do cells conduct nerve regeneration
- they are important for the process of repair
- they divide and make a new portion of axons to be made
- need more Schwann cells to do the myelination
- also secrete neurotrophic factors to guide the axons
what are the obstacles to successful regernation
Prolonged axotomy (severing) reduces
the number of neurons and axons that
can regenerate.
After 1 month: Schwann cells
down-regulate regeneration associated
factors.
Prolonged denervation causes muscle
atrophy and fibrosis.
The proximal and distal part…
proximal part and distal part are often
connected with surgery. This should be done
within three weeks of injury.
what do the macrophages and microglia do after a primary injury
Macrophages and microglia will engulf debris and the injury site becomes walled off by a glial scar
what chemicals does the glial scar express
- Expresses chemicals that inhibit axon growth – chondroitin sulphate proteoglycans
why is the glial scar good and why is it bad
GOOD: because it engulfs debris, seals lesion site and repairs
BBB
BAD: physical and chemical barrier for neurodegeneration
(inhibits axon growth).
what is the sporting response
- this happens at the glial scar
- axons will try and grow through glial
scar but this fails.
what are the two main barriers to CNS repair
Hostile environment
- Scar tissue – physical and chemical barrier
- Myelin – associated inhibitory proteins
Poor regenerative response
what are examples of some myelin inhibitor proteins
– Nogo protiens, MAG (myelin-associated glycoprotein), Omgp ( oligodendrocyte myelin glycoprotein
what are solutions to CNS repair
- neuroprotection
- promotion of axonal regernation
- guiding axonal regrowth
describe neuroprotection
to contain the effects of early trauma, inflammation, and scar formation
Omega-3 polyunsaturated fatty acids
describe promotion of axonal regeneration
• positive trophic support
Growth factors
Cell / tissue transplantation (olfactory ensheathing cells, Schwann cells, fetal tissue, stem cells)
• counteracting inhibitory influences
Enzymes to target inhibitory proteoglycans
Inhibitory antibodies to target myelin inhibitory proteins
describer guiding axonal regrowth
to re-establish appropriate connectivities
- Biomaterial scaffolds (nerve guidance channels; hydrogels
