Basic fibroblast growth factor promotes neuronal survival but not behavioral recovery in the transected and Schwann cell implanted rat thoracic spinal cord

J Neurotrauma. 2004 Oct;21(10):1415-30. doi: 10.1089/neu.2004.21.1415.

Abstract

It was investigated whether the addition of basic fibroblast growth factor (FGF-2) enhances the efficacy of a Schwann cell (SC) bridge to repair the transected spinal cord by assessing tissue sparing and neuronal survival near the graft-cord interfaces, axonal regeneration and myelination in the graft, and behavioral recovery up to 12 weeks post-grafting. Experimental animals received a bridge of SCs within fibrin containing 1 microg of FGF-2; control animals received a SC implant without FGF-2. Sparing of tissue in a 2.5-mm-long segment near the graft-cord borders was 69% in the rostral and 52% in the caudal cord at 6 weeks post-grafting, not significantly different from the control group. With FGF-2, survival of NeuN-positive cells was increased in the rostral cord: 24.4%, 20.4%, and 17.2% of the number of positive cells in the uninjured cord compared to 13.5%, 9.1%, and 8.9% in controls at 3, 6, and 12 weeks post-grafting, respectively. Similarly, in the caudal cord, survival of NeuN-positive cells was increased with FGF-2: 19.3%, 16.8%, and 14.5% compared to 10.8%, 5.6%, and 6.1% in controls. The staining intensity of glial fibrillary acidic protein was significantly higher at the interfaces of both cord stumps at 3 weeks with SC/FGF-2 grafts; chondroitin sulfate proteoglycan (CS-56) staining was more intense in the rostral cord but only at 6 weeks. Blood vessels in the FGF-2 grafts were larger and less regular in shape than those in control grafts. Axonal growth into the bridge was not improved by the addition of FGF-2. Retrogradely traced neurons were not found rostral to the implant, indicating that axons had not grown a few mm into the caudal spinal tissue. Recovery of hind limb function was similar in both groups. Despite the neuroprotective effects of FGF-2, improved effects on axonal regeneration and functional recovery were not observed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Cell Transplantation
  • Chondroitin Sulfates / metabolism
  • Female
  • Fibroblast Growth Factor 2 / therapeutic use*
  • Glial Fibrillary Acidic Protein / drug effects
  • Glial Fibrillary Acidic Protein / metabolism
  • Immunohistochemistry
  • Microscopy, Electron, Transmission
  • Nerve Regeneration / drug effects
  • Neurons / drug effects*
  • Neurons / pathology
  • Neurons / ultrastructure
  • Rats
  • Rats, Inbred F344
  • Schwann Cells / transplantation*
  • Schwann Cells / ultrastructure
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / surgery*
  • Thoracic Vertebrae / drug effects
  • Thoracic Vertebrae / surgery

Substances

  • Glial Fibrillary Acidic Protein
  • Fibroblast Growth Factor 2
  • Chondroitin Sulfates