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

被引:61
作者
Meijs, MFL
Timmers, L
Pearse, DD
Tresco, PA
Bates, ML
Joosten, EAJ
Bunge, MB
Oudega, M
机构
[1] Univ Miami, Sch Med, Miami Project Cure Paralysis, Miami, FL 33136 USA
[2] Univ Miami, Sch Med, Dept Neurol Surg, Miami, FL 33136 USA
[3] Univ Miami, Sch Med, Dept Cell Biol & Anat, Miami, FL 33136 USA
[4] Univ Utah, Keck Ctr Tissue Engn, Salt Lake City, UT USA
[5] Univ Maastricht, Dept Cellular Neurosci, Maastricht, Netherlands
关键词
chondroitin sulfate proteoglycan; CNS; glial fibrillary acidic protein; spinal cord injury; transplantation;
D O I
10.1089/neu.2004.21.1415
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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 mug 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.
引用
收藏
页码:1415 / 1430
页数:16
相关论文
共 89 条
[61]  
Oudega M, 1999, BIOMED REV, V10, P75
[62]  
OUDEGA M, 2001, METHODS TISSUE ENG, P1143
[63]   REGROWTH OF AXONS IN LESIONED ADULT-RAT SPINAL-CORD - PROMOTION BY IMPLANTS OF CULTURED SCHWANN-CELLS [J].
PAINO, CL ;
FERNANDEZVALLE, C ;
BATES, ML ;
BUNGE, MB .
JOURNAL OF NEUROCYTOLOGY, 1994, 23 (07) :433-452
[64]   ESTABLISHMENT OF ADULT-RAT SCHWANN-CELL CULTURES - EFFECT OF B-FGF, ALPHA-MSH, NGF, PDGF, AND TGF-BETA ON CELL-CYCLE [J].
PEULVE, P ;
LAQUERRIERE, A ;
PARESY, M ;
HEMET, J ;
TADIE, M .
EXPERIMENTAL CELL RESEARCH, 1994, 214 (02) :543-550
[65]  
PLANT GW, 2001, NEUROL DIS, V52, P529
[66]   Basic fibroblast growth factor (bFGF) enhances tissue sparing and functional recovery following moderate spinal cord injury [J].
Rabchevsky, AG ;
Fugaccia, I ;
Fletcher-Turner, A ;
Blades, DA ;
Mattson, MP ;
Scheff, SW .
JOURNAL OF NEUROTRAUMA, 1999, 16 (09) :817-830
[67]   Basic fibroblast growth factor (bFGF) enhances functional recovery following severe spinal cord injury to the rat [J].
Rabchevsky, AG ;
Fugaccia, I ;
Turner, AF ;
Blades, DA ;
Mattson, MP ;
Scheff, SW .
EXPERIMENTAL NEUROLOGY, 2000, 164 (02) :280-291
[68]   ACTIVATION OF PHOSPHATIDYLINOSITOL 3-KINASE BY EPIDERMAL GROWTH-FACTOR, BASIC FIBROBLAST GROWTH-FACTOR, AND NERVE GROWTH-FACTOR IN PC12 PHEOCHROMOCYTOMA CELLS [J].
RAFFIONI, S ;
BRADSHAW, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (19) :9121-9125
[69]   Olfactory ensheathing glia:: Properties and function [J].
Ramón-Cueto, A ;
Avila, J .
BRAIN RESEARCH BULLETIN, 1998, 46 (03) :175-187
[70]   Alterations in fibroblast growth factor receptor expression following brain injury [J].
Reilly, JF ;
Kumari, VG .
EXPERIMENTAL NEUROLOGY, 1996, 140 (02) :139-150