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The effects of FK506 on dorsal column axons following spinal cord injury in adult rats: Neuroprotection and local regeneration

Bavetta, S; Hamlyn, PJ; Burnstock, G; Lieberman, AR; Anderson, PN; (1999) The effects of FK506 on dorsal column axons following spinal cord injury in adult rats: Neuroprotection and local regeneration. EXP NEUROL , 158 (2) 382 - 393.

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Abstract

There is considerable evidence that immunophilin ligands can promote the regeneration of axons in peripheral nerves and act as neuroprotective agents in the CNS. We have examined the effects of FK506 and GPI 1046 on the responses to partial transection of ascending spinal dorsal column axons at T9, in some cases combined with crush of one sciatic nerve. FK506 (0.5 or 2.0 mg/kg) and GPI 1046 (10 or 40 mg/kg) was administered subcutaneously immediately after surgery and five times a week thereafter. Some animals received methylprednisolone (MP) (two subcutaneous doses of 30 mg/kg) in addition to, or instead of, FK506. After survival times of 1-12 weeks, dorsal column axons were labeled transganglionically with cholera toxin B-HRP. There was massive axonal sprouting at the lesion sites in animals with sciatic nerve injury and immunophilin ligand treatment. In FK506-treated animals a few severed sensory axons regenerated for up to 10 mm rostral to the lesion. Of greater significance, 30% of 71 FK506-treated animals had spared axons in the dorsal column, extending to the nucleus gracilis, versus 8% of 50 control animals (P < 0.05), showing that FK506 reduces the likelihood of axonal destruction due to secondary injury. A combination of FK506 and MP afforded greater protection than MP alone (P < 0.05), but axonal survival was not affected by sciatic nerve crush, dose of FK506, or survival time after injury. GPI 1046 (n = 11) did not promote axonal survival. Thus FK506 protects axons from secondary injury following spinal cord trauma, and in this experimental model, its neuroprotective effect is greater than that of MP. (C) 1999 Academic Press.

Type: Article
Title: The effects of FK506 on dorsal column axons following spinal cord injury in adult rats: Neuroprotection and local regeneration
Keywords: FK506, immunophilin ligands, spinal cord injury, axon regeneration, neuroprotection, PERIPHERAL-NERVE INJURY, CYCLOSPORINE-A, IMMUNOSUPPRESSANT FK506, SCIATIC-NERVE, NITRIC-OXIDE, GLUTAMATE NEUROTOXICITY, DOPAMINERGIC-NEURONS, IMMUNOPHILIN LIGANDS, FUNCTIONAL RECOVERY, HIPPOCAMPAL-NEURONS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: http://discovery.ucl.ac.uk/id/eprint/113314
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