Peripheral nerve grafts and aFGF restore partial hindlimb function in adult paraplegic rats.
The purpose of this study was to evaluate the degree of functional recovery in adult rats with completely transected spinal cord following experimental treatment regimens that include implantation of peripheral nerve segments and local application of acidic fibroblast growth factor (aFGF). Rats were randomly divided to five groups: (1) spinal cord transection, (2) spinal cord transection and aFGF treatment, (3) spinal cord transection and peripheral nerve grafts, (4) spinal cord transection, aFGF treatment, and peripheral nerve grafts, and (5) sham control (laminectomy only). The locomotor behavior of all rats was analyzed by the Basso, Beattie and Bresnahan (BBB) open field locomotor test over the six months survival time. Immunohistochemisty for neurofilament protein, and somatosensory (SSEP) and motor evoked potentials (MEP) were used to evaluate axon growth across the damage site following the different treatments. The results show four principal findings: (1) Only the combination of peripheral nerve grafts and aFGF treatment improved hindlimb locomotor function after spinal cord transection. (2) The SSEP and MEP demonstrated electrophysiological evidence of both sensory and motor information crossing the damaged site, but only in the combined nerve grafts and aFGF treatment rats. (3) Immunostaining demonstrated neurofilament positive axons extending through the graft area and into distal end of spinal cord, but only in the group with combined nerve grafts and aFGF treatment. (4) Retransection of group 4 rats eliminated the behavioral recovery, MEP, and SSEP responses, indicating that the improvement of hindlimb locomotor activity came from supraspinal control. These results demonstrate the ability of the repair strategy combining peripheral nerve grafts and aFGF treatment to facilitate the regeneration of spinal ascending and descending tracts and also recovery of motor behavior following spinal cord injury.
Lee
Yu-Shang
YS
Department of Anatomy and Neurobiology, College of Medicine, University of California, Irvine, USA.
Hsiao
Ian
I
Lin
Vernon W
VW
D000818:Animals; D001369:Axons / Q000737:chemistry; D001522:Behavior, Animal; D019054:Evoked Potentials, Motor; D005073:Evoked Potentials, Somatosensory; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D006614:Hindlimb / Q000502:physiology; D007367:Intercostal Nerves / Q000637:transplantation*; D009043:Motor Activity; D009416:Nerve Regeneration / Q000187:drug effects; D016900:Neurofilament Proteins / Q000032:analysis; D010264:Paraplegia / Q000188:drug therapy* / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000601:surgery
D016900:Neurofilament Proteins; D016220:Fibroblast Growth Factor 1