Immunosuppressants: neuroprotection and promoting neurological recovery following peripheral nerve and spinal cord lesions.
No clinical techniques induce restoration of neurological losses following spinal cord trauma. Peripheral nerve damage also leads to permanent neurological deficits, but neurological recovery can be relatively good, especially if the ends of a transected nerve are anastomosed soon after the injury. The time until recovery generally depends on the distance the axons must regenerate to their targets. Neurological recovery following the destruction of a length of a peripheral nerve requires a graft to bridge the gap that is permissive to, and promotes, axon regeneration. But neurological recovery is slow and limited, especially for gaps longer than 1.5 cm, even using autologous peripheral nerve grafts. Without a reliable means of bridging long nerve gaps, such injuries commonly result in amputations. Promoting extensive neurological recovery requires techniques that simultaneously provide protection to injured neurons and increase the numbers of neurons that extend axons, while inducing more rapid and extensive axon regeneration across long nerve gaps. Although conduits filled with various materials enhance axon regeneration across short nerve gaps, pure sensory nerve graft remains the gold standard for use across long nerve gaps, even though they lead to only limited neurological recovery. Consistent results demonstrate that several immunosuppressive agents enhance the number of axons and the rate at which they regenerate. This review examines the roles played by immunosuppressants, especially FK506, with primary focus on its role as a neuroprotectant and neurotrophic agent, and its potential clinical use to promote improved neurological recovery following peripheral nerve and spinal cord injuries.
Sosa
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Section of Neurosurgery, Medical Sciences Campus, UPR, 201 Boulevard del Valle, San Juan 00901, Puerto Rico.
Reyes
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Kuffler
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DP
D000818:Animals; D001369:Axons / Q000187:drug effects; D004334:Drug Administration Schedule; D006801:Humans; D020104:Immunophilins / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007511:Ischemia / Q000188:drug therapy; D009416:Nerve Regeneration / Q000187:drug effects*; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D016559:Tacrolimus / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D020104:Immunophilins; D016559:Tacrolimus