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Journal of Neuroscience, Vol 10, 3594-3603, Copyright © 1990 by Society for Neuroscience
Inhibition of neurite outgrowth on astroglial scars in vitro
JS Rudge and J Silver
Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106.
Traumatic injury to the adult mammalian CNS results in the formation of an
astroglial-mesenchymal scar that seals the wound site but blocks axonal
regeneration in the process. The mechanism that leads to this inhibition of
axon outgrowth has been proposed to be either a physical barrier blocking
the advancement of the growth cone or chemical factors actively inhibiting
axon outgrowth. At present, it is unknown whether one or both of these
mechanisms are responsible for the inhibitory nature of the glial scar in
vivo. Using a model of CNS trauma that allows for removal of an adult rat
glial scar intact on a nitrocellulose support and placement in vitro with
the upper surface exposed, we addressed the question of whether the
inhibitory effects could be accounted for by chemical components at the
scar surface. A purified population of rat hippocampal neurons was seeded
onto the scar explants as well as onto explants taken from neonatal rat
cerebral cortex, and the extent of neurite outgrowth was compared. We found
that the glial scar, at best, stimulates only minimal neurite outgrowth
over its surface when compared to the immature environment explanted in the
same manner. This growth-inhibitory state cannot merely be explained by
neuronotoxic factors or fibroblasts preventing astrocyte-mediated neurite
outgrowth. The inhibition is more probably due to the expression of
molecules on the surface of the adult scar that either directly inhibit
growth cones or inhibit them indirectly by occluding neurite-promoting
factors in the extracellular matrix or on the astrocyte surface.
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