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Regeneration of nigrostriatal dopaminergic axons by degradation of chondroitin sulfate is accompanied by elimination of the fibrotic scar and glia limitans in the lesion site.

Abstract
Chondroitin sulfate increases around a lesion site after central nervous system injury and is believed to be an impediment to axonal regeneration, because administration of chondroitinase ABC, a chondroitin sulfate-degrading enzyme, promotes axonal regeneration of central neurons. To examine the physiological role of chondroitin sulfate up-regulation after injury, the nigrostriatal dopaminergic axons were unilaterally transected in mice, and chondroitinase ABC was then injected into the lesion site. In mice transected only, tyrosine hydroxylase-immunoreactive axons did not extend across the lesion at 1 or 2 weeks after the transection. Immunoreactivities of chondroitin sulfate side chains and core protein of NG2 proteoglycan increased in and around the lesion site, and a fibrotic scar containing type IV collagen deposits developed in the lesion center. In contrast, in mice transected and treated with chondroitinase ABC, numerous tyrosine hydroxylase-immunoreactive axons were regenerated across the lesion at 1 and 2 weeks after the transection. In these animals, chondroitin sulfate immunoreactivity remarkably decreased, and immunoreactivity of 2B6 antibody, which recognizes the stub of degraded chondroitin sulfate side chains, was enhanced. Furthermore, the formation of a fibrotic scar and a glia limitans that surrounds the former was completely prevented, although type IV collagen immunoreactivity remained in newly formed blood capillaries around the lesion site. We discuss the question of whether the chondroitin sulfate is acting as a direct inhibitor of axonal regeneration or whether the observed changes are due to a prevention of the fibrotic scar formation and a rearrangement of astrocytic membranes.
AuthorsHong-Peng Li, Akiko Homma, Kazunori Sango, Koki Kawamura, Geoffrey Raisman, Hitoshi Kawano
JournalJournal of neuroscience research (J Neurosci Res) Vol. 85 Issue 3 Pg. 536-47 (Feb 15 2007) ISSN: 0360-4012 [Print] United States
PMID17154415 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Chondroitin Sulfates
  • Chondroitin ABC Lyase
  • Dopamine
Topics
  • Animals
  • Axons (physiology)
  • Brain Injuries (physiopathology)
  • Chondroitin ABC Lyase (metabolism)
  • Chondroitin Sulfates (metabolism)
  • Cicatrix
  • Corpus Striatum (physiology)
  • Dopamine (physiology)
  • Male
  • Mice
  • Mice, Inbred ICR
  • Models, Animal
  • Nerve Regeneration (physiology)
  • Neuroglia (pathology)
  • Substantia Nigra (physiology)

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