Administration of chondroitinase ABC rostral or caudal to a spinal cord injury site promotes anatomical but not functional plasticity

J Neurotrauma. 2009 Dec;26(12):2323-33. doi: 10.1089/neu.2009.1047.

Abstract

Growth-inhibitory chondroitin sulfate proteoglycans (CSPG) are a primary target for therapeutic strategies after spinal cord injury because of their contribution to the inhibitory nature of glial scar tissue, a major barrier to successful axonal regeneration. Chondroitinase ABC (ChABC) digestion of CSPGs promotes axonal regeneration beyond a lesion site with subsequent functional improvement. ChABC also has been shown to promote sprouting of spared fibers but it is not clear if functional recovery results from such plasticity. Here we sought to better understand the roles rostral or caudal sprouting may play in ChABC-mediated functional improvement. To achieve this, ChABC or vehicle was injected rostral or caudal to a unilateral C5 injury. When injected rostral to a hemisection, ChABC promoted significant sprouting of 5HT+ fibers into dorsal and ventral horns. When ChABC was injected into tissue caudal to a hemisection, no additional sprouting was observed. When injected caudal to a hemicontusion injury, ChABC promoted sprouting of 5HT+ fibers into the ventral horn but not the dorsal horn. None of this sprouting resulted in a change in the synaptic component synapsin, nor did it impact performance in behavioral tests assessing motor function. These data suggest that ChABC-mediated sprouting of spared fibers does not necessarily translate into functional recovery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anterior Horn Cells / physiology
  • Chondroitin ABC Lyase / pharmacology*
  • Chondroitin ABC Lyase / therapeutic use
  • Cicatrix / drug therapy
  • Cicatrix / enzymology
  • Cicatrix / physiopathology
  • Disease Models, Animal
  • Efferent Pathways / drug effects
  • Efferent Pathways / metabolism
  • Female
  • Gliosis / drug therapy
  • Gliosis / enzymology
  • Gliosis / physiopathology
  • Growth Cones / drug effects*
  • Growth Cones / metabolism
  • Growth Inhibitors / antagonists & inhibitors
  • Growth Inhibitors / metabolism
  • Nerve Regeneration / drug effects*
  • Nerve Regeneration / physiology
  • Neuronal Plasticity / drug effects*
  • Neuronal Plasticity / physiology
  • Paralysis / drug therapy
  • Raphe Nuclei / cytology
  • Raphe Nuclei / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects
  • Recovery of Function / physiology
  • Serotonin / metabolism
  • Spinal Cord / drug effects*
  • Spinal Cord / enzymology
  • Spinal Cord / physiopathology
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / enzymology
  • Spinal Cord Injuries / physiopathology
  • Synapsins / metabolism

Substances

  • Growth Inhibitors
  • Synapsins
  • Serotonin
  • Chondroitin ABC Lyase