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Chondroitinase ABC enhances axonal regrowth through Schwann cell-seeded guidance channels after spinal cord injury.

Abstract
Grafting of Schwann cell-seeded channels into hemisected adult rat thoracic spinal cords has been tested as a strategy to bridge the injured cord. Despite success in guiding axonal growth into the graft, regeneration across the distal graft-host interface into the host spinal cord was limited. We hypothesized that chondroitin sulfate (CS) glycoforms deposited at the gliotic front of the interface constitute a molecular barrier to axonal growth into the host cord. Because CS glycoforms deposited by purified astrocytes in vitro were removable by digestion with chondroitinase ABC, we attempted to achieve likewise by infusion of the enzyme to the host side of the interface. By 1 month post-treatment, significant numbers of regenerating axons crossed an interface that was subdued in macrophage/microglia reaction and decreased in CS-immunopositivity. The axons extended as far into the caudal cord as 5 mm, in contrast to nil in vehicle-infused controls. Fascicular organizations of axon-Schwann cell units within the regenerated tissue cable were better-preserved in enzyme-treated cords than in vehicle-infused controls. We conclude that CS glycoforms deposited during gliosis at the distal graft-host interface could be cleared by the in vivo action of chondroitinase ABC to improve prospects of axonal regeneration into the host spinal cord.
AuthorsC H Chau, D K Y Shum, H Li, J Pei, Y Y Lui, L Wirthlin, Y S Chan, X-M Xu
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 18 Issue 1 Pg. 194-6 (Jan 2004) ISSN: 1530-6860 [Electronic] United States
PMID14630702 (Publication Type: Journal Article)
Chemical References
  • Chondroitin Sulfates
  • Chondroitin ABC Lyase
Topics
  • Animals
  • Astrocytes (physiology)
  • Axons (drug effects, physiology, ultrastructure)
  • Blotting, Western
  • Chondroitin ABC Lyase (pharmacology)
  • Chondroitin Sulfates (analysis, immunology, metabolism)
  • Macrophages (physiology)
  • Myelin Sheath (physiology)
  • Nerve Regeneration (drug effects)
  • Rats
  • Schwann Cells (transplantation)
  • Spinal Cord (cytology, physiology)

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