Neuroimmunophilin Ligands Improve Functional Recovery and Increase Axonal Growth after Spinal Cord Hemisection in Rats
| Autor: | Takayuki Yamaji, Jan Voda, Bruce G. Gold |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
Red nucleus medicine.medical_treatment Central nervous system Functional Laterality Tacrolimus Rats Sprague-Dawley Lesion medicine Animals Saline Spinal Cord Injuries Red Nucleus business.industry Regeneration (biology) Axotomy Recovery of Function Anatomy Spinal cord Immunohistochemistry Axons Nerve Regeneration Rats Neuroprotective Agents medicine.anatomical_structure Microscopy Fluorescence Spinal Cord Peripheral nervous system Neurology (clinical) medicine.symptom business |
| Zdroj: | Journal of Neurotrauma. 22:1150-1161 |
| ISSN: | 1557-9042 0897-7151 |
| DOI: | 10.1089/neu.2005.22.1150 |
| Popis: | We have previously shown that FK506 accelerates the rate of nerve regeneration in the peripheral nervous system (PNS) and increases regeneration of central nervous system (CNS) axons into a peripheral nerve graft. In the present study, we examined whether FK506 and a nonimmunosuppressive derivative (FK1706) improve functional recovery and long distance regeneration following a hemisection lesion of spinal cord at T10/T11. Rats were given daily subcutaneous injections of either FK506 (2 mg/kg/day), FK1706 (2 mg/kg/day), an equivalent volume of saline or 30% DMSO as vehicle, respectively. Functional recovery was assessed using a modified Tarlov/Klinger scale, walking along progressively narrower wooden beams (7.7-1.7 cm widths), and analysis of footprints obtained during walking. Compared to both control groups, FK506 and FK1706-treated animals demonstrated significant functional recovery 4 days (beam walking), 2 weeks (footprints), and 4 weeks (Tarlov/Klinger scale). By 11 weeks, FK506-treated and FK1706-treated animals were able to walk, albeit poorly, along even the narrowest (1.7 cm) beam. At 11 weeks, the spinal cords were re-exposed and a small piece of gel foam-soaked Fluoro-Gold was placed on the injured side 2-cm caudal to the first injury. Five days later, the animals were perfused and tissues prepared for fluorescence microscopy. FK506-treated and FK1706-treated rats demonstrate a significantly greater number of retrogradely labeled neurons in the red nucleus. The results implicate a nonimmunosuppressant mechanism in FK506's action and suggest that FK506 or a nonimmunosuppressant derivative may be useful for treatment of spinal cord injuries. |
| Databáze: | OpenAIRE |
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