Trophic factors (like NGF) prevent the degeneration of peripheral nerves after Axotomy
Macrophages stimulate proliferation of Schwann cells which secrete other neurotrophic factors (like laminin and fibronectin)
PNS regeneration can occur through semipermeable synthetic channels
Regeneration does not occur in the CNS
Why? – Some theories:
Glial scar blocks regeneration
a gap is formed between transected nerve where there is a loss of neurotrophic and tropic factors, inflammation can widen the gap
excess of neurotrophic factors (NGF, BGF, etc.) causes the nerve to stay where it is and not regenerate. Can
Ý survival rate of cell bodies. Excess sprouting of neurons and can become "addicted" to the area.
active repulsion by inhibitory proteins like N135, N1250 and nogo on oligodenrocytes. Antibody to nogo (IN-1) can allow for regeneration. Inhibitory proteoglycans on reactive astroglia may also inhibit growth.
the distal olfactory system of the CNS is capable of regeneration
the dorsal root entry zone of the spinal cord is a model of regenerative failure
Proteoglycans
large molecules, GAG side chains (sugars), can inhibit cell migration (cancer cells can’t migrate through proteoglycans)
high negative charge and water content can repel Cell Adhesion Molecules (CAM)
growth cone is driven by cell adhesion molecules
GAG receptors might inhibit CAM receptors
these can be used to build a barrier to regeneration and avoid adhesions during surgery
chondroitin sulfate can be used to dissolve the sugar side groups of the proteoglycans and permit nerve regeneration
Current Research
the bottom line was that glial scarring stops regeneration of nerves in the CNS by proteoglycans
white columns can be regenerated
reactive astrocytes causing gliosis and production of GFAP can be good or bad
Good – can overcome potent inhibition of myelin produced by oligodendrocytes
Bad – cause glial scarring
The future will look to constructive neurosurgery instead of destructive (taking things out of the head)
Ideas for Fostering Regeneration
(1) Experiments using peripheral nerve, ensheathing cells or embryonic grafts as bridges
(2) Experiments using IN-1 antibodies
(3) Microtransplantation experiments showing robust potential for regeneration and importance of glial scar