Basic fibroblast growth factor promotes neuronal survival but not behavioral recovery in the transected and Schwann cell implanted rat thoracic spinal cord.
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.
Meijs
Matthijs F L
MF
The Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, Florida 33136, USA.
Timmers
Leonardus
L
Pearse
Damien D
DD
Tresco
Patrick A
PA
Bates
Margaret L
ML
Joosten
Elbert A J
EA
Bunge
Mary Bartlett
MB
Oudega
Martin
M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D017690:Cell Transplantation; D002809:Chondroitin Sulfates / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D005904:Glial Fibrillary Acidic Protein / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D009416:Nerve Regeneration / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D011916:Rats, Inbred F344; D012583:Schwann Cells / Q000637:transplantation* / Q000648:ultrastructure; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D013904:Thoracic Vertebrae / Q000187:drug effects / Q000601:surgery
D005904:Glial Fibrillary Acidic Protein; D016222:Fibroblast Growth Factor 2; D002809:Chondroitin Sulfates