Chondroitinase ABC Promotes Functional Recovery After Spinal Cord Injury

Nature. 2002 Apr 11;416(6881):636-40. doi: 10.1038/416636a.

Abstract

The inability of axons to regenerate after a spinal cord injury in the adult mammalian central nervous system (CNS) can lead to permanent paralysis. At sites of CNS injury, a glial scar develops, containing extracellular matrix molecules including chondroitin sulphate proteoglycans (CSPGs). CSPGs are inhibitory to axon growth in vitro, and regenerating axons stop at CSPG-rich regions in vivo. Removing CSPG glycosaminoglycan (GAG) chains attenuates CSPG inhibitory activity. To test the functional effects of degrading chondroitin sulphate (CS)-GAG after spinal cord injury, we delivered chondroitinase ABC (ChABC) to the lesioned dorsal columns of adult rats. We show that intrathecal treatment with ChABC degraded CS-GAG at the injury site, upregulated a regeneration-associated protein in injured neurons, and promoted regeneration of both ascending sensory projections and descending corticospinal tract axons. ChABC treatment also restored post-synaptic activity below the lesion after electrical stimulation of corticospinal neurons, and promoted functional recovery of locomotor and proprioceptive behaviours. Our results demonstrate that CSPGs are important inhibitory molecules in vivo and suggest that their manipulation will be useful for treatment of human spinal injuries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Axons / pathology
  • Chondroitin ABC Lyase / metabolism*
  • Chondroitin ABC Lyase / therapeutic use*
  • Electrophysiology
  • GAP-43 Protein / metabolism
  • Ganglia, Spinal / injuries
  • Ganglia, Spinal / metabolism
  • Ganglia, Spinal / pathology
  • Humans
  • Isoenzymes / metabolism
  • Male
  • Motor Activity
  • Nerve Crush
  • Nerve Regeneration / physiology*
  • Neurons / metabolism
  • Neurons / pathology
  • Protein Kinase C / metabolism
  • Psychomotor Performance
  • Rats
  • Rats, Wistar
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / physiopathology*
  • Spinal Cord Injuries / therapy*
  • Up-Regulation

Substances

  • GAP-43 Protein
  • Isoenzymes
  • protein kinase C gamma
  • Protein Kinase C
  • Chondroitin ABC Lyase