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The Journal of Neuroscience, July 15, 1999, 19(14):5810-5822
Robust Regeneration of Adult Sensory Axons in Degenerating White
Matter of the Adult Rat Spinal Cord
Stephen J. A.
Davies,
David R.
Goucher,
Catherine
Doller, and
Jerry
Silver
Department of Neurosciences, Case Western Reserve University School
of Medicine, Cleveland, Ohio 44106
We have recently reported that minimally disturbed adult CNS white
matter can support regeneration of adult axons by using a novel
microtransplantation technique to inject minute volumes of dissociated
adult rat dorsal root ganglion neurons directly into adult rat
CNS pathways (Davies et al., 1997). This atraumatic injection procedure
minimized scarring and allowed considerable numbers of regenerating
adult axons immediate access to the adult CNS glial terrain where they
rapidly extended for long distances. A critical question remained as to
whether degenerating white matter at acute and chronic stages (up to 3 months) after injury could still support regeneration. To investigate
this, we have microtransplanted adult sensory neurons into degenerating
white matter of the adult rat spinal cord several millimeters rostral to a severe lesion of the dorsal columns. Regeneration of donor sensory
axons in both directions away from the site of transplantation was
robust even within white matter undergoing fulminant Wallerian degeneration despite intimate contact with myelin. Along their route,
the regrowing axons extended large numbers of collaterals into the
adjacent dorsal horn. However, after entering the lesion, the rapidly
extending growth cones stopped and became dystrophic within high
concentrations of reactive glial matrix. Our results offer compelling
evidence that the major environmental impediment to regeneration in the
adult CNS is the molecular barrier that forms directly at the lesion
site, and that degenerating white matter beyond the glial scar has a
far greater intrinsic ability to support axon regeneration than
previously thought possible.
Key words:
spinal cord; regeneration; inhibitory proteoglycans; transplantation; reactive astrocytes; glial scar; growth cone; myelin
inhibition; extracellular matrix
Copyright © 1999 Society for Neuroscience 0270-6474/99/19145810-13$05.00/0
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M. I. Romero, N. Rangappa, L. Li, E. Lightfoot, M. G. Garry, and G. M. Smith
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