Flashcards in Neural Regeneration Deck (16):
true/false neither CNS or PNS neurons can regenerate
False, when peripheral axons are damaged, the proximal portions can partially or completely regenerate distally. (cell body can be in PNS or CNS).
what process tends to inhibit regeneration of central axons/neurons
glial scar formation
what can be expected up to 2 weeks post PNS axonal injury?
loss of nissl substance (chromolysis)
-degen of axon and myelination sheath below the site of injury
-->debris phagocytosed by macrophage influx
-->Muscle Fibre Atrophy
What happens 3wks post PNS axonal injury
schwann cell proliferation, creating compact cord.
growing axon penetrates the compact cord.
-->muscle fibre atrophy continues
What can happen 3 months post PNS axonal injury? (successful cases)
-electrical activity restored
--->muscle fibre regeneration!
What can happen 3 months post PNS axonal injury? (unsuccessful cases)
neuroma formation, bundling of axon at the site of injury
-->muscle fibre atrophied
T/F crushed and cut axons regenerate at the same rate
FALSE. repair is faster if axon is crushed rather than cut.
-the better preserved the axonal alignment the easier is to regenerate.
-in cut axons some may regenerate incorrectly, end up servicing the wrong conduits.
details of primary CNS spinal cord injury (incl Tx)
injury due to physical damage -->cellular loss
Tx to minimize extent of primary damage. (ex tissue plasminogen activator for stroke)
details of secondary CNS spinal cord injury in short term (minutes/hours)
-Ca 2+ influx
-lipid peroxidation & free radical production
details of secondary CNS spinal cord injury over hours to days/weeks
-immune cell infiltration, microglial activation
-cytokines, chemokines, metalloproteases
details of secondary CNS spinal cord injury over days/weeks
-apoptosis - neuronal and oligendendroglial
-astrocytic gliosis and glial scar formation
-syrinx cavity formation and meningeal fibroblast migration
strategies to repair the CNS?
-protect surviving cells
-regrowth of surviving neurons & remyelination
-modulate astrocytic gliosis (wound repair and scar formation)
-neural stem cells (mobilise endogenous cells, transplant exogenous cells)
what factors impede axonal regeneration and how to tx?
Problem: lack of trophic support
Solution: encourage axons to grow by providing growth promoting factors (neurotrophin: NGF, BDNF)
Prob: axon regrowth inhibited by wound environment
Soln: inhibit growth blocking factors. Ie astrocytic gliosis and glial scar; myelin inhibitors; developmental guidance molecules
Axonal plasticity vs axonal regeneration?
Plasticity described compensation by other uninjured axons to branch and service the conduits previously innervated by the injured axon.-->"axonal sprouting"
regeneration is complete renewal of injured axon
what does astrocytic gliosis cause?
-upregulate astrocyte cytoskeleton proteins (GFAP).
-secrete ECM (chondroiton sulfate proteoglycans)
-secrete cytokines (IL-1, TNF-alpha) and growth factors (NGF/BDNF)
-increase expression of development axon guidance molecules
-->glial scar formation-->forms a barrier between injury site and healthy site