Motor recovery and anatomical evidence of axonal regrowth in spinal cord-repaired adult rats.
Behavioral assessments of hindlimb motor recovery and anatomical assessments of extended axons of long spinal tracts were conducted in adult rats following complete spinal cord transection. Rats were randomly divided into 3 groups: 1) sham control group (laminectomy only; n = 12); 2) transection-only group, spinal cord transection at T8 (n = 20); and 3) experimental treatment group, spinal cord transection at T8, with peripheral nerve grafts (PNG) and application of acidic fibroblast growth factor (aFGF) (n = 14). The locomotor behavior and stepping of all rats were analyzed over a 6-month survival time using the Basso, Beattie, Bresnahan (BBB) open field locomotor test and the contact placing test. Immunohistochemistry for serotonin (5-HT), anterograde tracing with biotinylated dextran amine (BDA), and retrograde tracing with fluoro-gold were used to evaluate the presence of axons below the damage site following treatment. When compared with the transection-only group, the nerve graft with the aFGF group showed 1) significant improvement in hindlimb locomotion and stepping, 2) the presence of 5-HT-labeled axons below the lesion site at lumbar cord level (these were interpreted as regenerated axons from the raphe nuclei), 3) the presence of anterograde BDA labeling of corticospinal tract axons at the graft site and below, and 4) fluoro-gold retrograde labeling of neuron populations in motor cortex and in red nucleus, reticulospinal nuclei, raphe nuclei, and vestibular nuclei. We conclude that peripheral nerve grafts and aFGF treatments facilitate the regrowth of the spinal axons and improve hindlimb function in a T-8 spinal cord-transected rat model.
Lee
Yu-Shang
YS
Department of Anatomy, College of Medicine, University of California, Irvine, Irvine, California, USA.
Lin
Ching-Yi
CY
Robertson
Richard T
RT
Hsiao
Ian
I
Lin
Vernon W
VW
D000818:Animals; D001370:Axonal Transport / Q000187:drug effects / Q000502:physiology; D001710:Biotin / Q000031:analogs & derivatives*; D003911:Dextrans; D004525:Efferent Pathways / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D005260:Female; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005456:Fluorescent Dyes; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D010525:Peripheral Nerves / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy*; D013266:Stilbamidines; D016378:Tissue Transplantation / Q000379:methods*; D016896:Treatment Outcome
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D003911:Dextrans; D005456:Fluorescent Dyes; D013266:Stilbamidines; C076397:biotinylated dextran amine; D012701:Serotonin; D005346:Fibroblast Growth Factors; D001710:Biotin