title: Basic fibroblast growth factor promotes neuronal survival but not behavioral recovery in the transected and Schwann cell implanted rat thoracic spinal cord.
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.
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, Florida 33136, USA.
authors.forename: Matthijs F L
authors.initials: MF
authors.lastname: Meijs
authors.forename: Leonardus
authors.initials: L
authors.lastname: Timmers
authors.forename: Damien D
authors.initials: DD
authors.lastname: Pearse
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Tresco
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Bates
authors.forename: Elbert A J
authors.initials: EA
authors.lastname: Joosten
authors.forename: Mary Bartlett
authors.initials: MB
authors.lastname: Bunge
authors.forename: Martin
authors.initials: M
authors.lastname: Oudega
mesh_terms: 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
chemical_list: D005904:Glial Fibrillary Acidic Protein; D016222:Fibroblast Growth Factor 2; D002809:Chondroitin Sulfates