Stimulation of corticospinal tract regeneration in the chronically injured spinal cord.
Acute spinal cord injury models have proved popular in studies aimed at identifying factors capable of influencing axonal regeneration within the central nervous system. In these models, the test factors (e.g. graft tissues or cells, antibodies, growth factors, etc.) are typically administered at the time of spinal cord injury. In this study, we use a rat chronic spinal cord injury model to identify possible factors which can stimulate regeneration of the chronically lesioned corticospinal tract axons. We demonstrate that surgical grafting of segments of autologous, preligated sural nerve, into the syrinx, stimulates sprouting and regeneration of the corticospinal tract as evidenced by the presence of anterograde labelled corticospinal tract processes within the cavity walls two or more weeks after treatment. Regrowing corticospinal processes were not observed within control animals. The anterogradely labelled corticospinal tract axons were found exclusively within the central grey tissue comprising the cavity walls with no regrowing corticospinal process observed within the white matter. A similar pattern of regeneration was observed following injection into the cavity of a suspension of minced autologous preligated sural nerve. Evidence of corticospinal tract regeneration was seen when either wheat germ agglutinin--horseradish peroxidase or biotinylated--dextran was used as an anterograde tracer. These data demonstrate that the chronically injured cortical motor neurons retain the capacity to regenerate for extended periods and that regeneration can be stimulated using grafts of minced, preligated autologous peripheral nerve tissue.
Department of Human Physiology, Flinders University School of Medicine, GPO Box 2100 Adelaide SA 5001 Australia. i.ferguson@flinders.edu.au
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Ferguson
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Koide
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Rush
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D019771:Axotomy / Q000009:adverse effects; D001710:Biotin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016380:Brain Tissue Transplantation / Q000379:methods / Q000502:physiology*; D002908:Chronic Disease; D003911:Dextrans / Q000493:pharmacokinetics; D005260:Female; D006085:Graft Survival / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D011712:Pyramidal Tracts / Q000293:injuries* / Q000378:metabolism / Q000601:surgery*; D051381:Rats; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D013497:Sural Nerve / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate / Q000493:pharmacokinetics
D003911:Dextrans; D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; C076397:biotinylated dextran amine; D001710:Biotin