Robust regeneration of adult sensory axons in degenerating white matter of the adult rat spinal cord
TLDR
These 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.Abstract:
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.read more
Citations
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Regeneration beyond the glial scar
Jerry Silver,Jared H. Miller +1 more
TL;DR: Chondroitin and keratan sulphate proteoglycans are among the main inhibitory extracellular matrix molecules that are produced by reactive astrocytes in the glial scar, and they are believed to play a crucial part in regeneration failure.
Journal ArticleDOI
Chondroitinase ABC promotes functional recovery after spinal cord injury
Elizabeth J. Bradbury,Lawrence D. F. Moon,Lawrence D. F. Moon,Reena J Popat,V.R. King,GS Bennett,Preena N. Patel,James W. Fawcett,Stephen B. McMahon +8 more
TL;DR: It is demonstrated that CSPGs are important inhibitory molecules in vivo and suggested that their manipulation will be useful for treatment of human spinal injuries.
Journal ArticleDOI
Degeneration and regeneration of the nervous system
Journal ArticleDOI
Reactive astrocytes protect tissue and preserve function after spinal cord injury.
Jill R. Faulkner,Julia E. Herrmann,Michael J. Woo,Keith E. Tansey,Ngan B. Doan,Michael V. Sofroniew +5 more
TL;DR: The findings show that reactive astrocytes provide essential activities that protect tissue and preserve function after mild or moderate SCI, and suggest that identifying ways to preserve reactive astracytes, to augment their protective functions, or both, may lead to novel approaches to reducing secondary tissue degeneration and improving functional outcome after SCI.
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Glial inhibition of CNS axon regeneration
Glenn Yiu,Zhigang He +1 more
TL;DR: The molecular basis of inhibitory molecules in CNS myelin as well as proteoglycans associated with astroglial scarring are evaluated and their contributions to the limitation of long-distance axon repair and other types of structural plasticity are evaluated.
References
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Degeneration and regeneration of the nervous system
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Axonal elongation into peripheral nervous system "bridges" after central nervous system injury in adult rats
Samuel David,Albert J. Aguayo +1 more
TL;DR: The origin, termination, and length of axonal growth after focal central nervous system injury was examined in adult rats by means of a new experimental model and the regenerative potential of these central neurons seems to be expressed when the central nervous System glial environment is changed to that of the peripheral nervous system.
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Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes
TL;DR: The inability of the adult glial scar tissue to support neurite outgrowth was best correlated with the expression of CS-PG and CT, suggesting that these molecules may be involved in limiting the growth of regenerating axons in the CNS after injury.