Axonal regeneration in early stages of sciatic nerve crush injury is enhanced by α7nAChR in rats

This study investigated the role of alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) in axonal regeneration after crush injury to the rat sciatic nerve. The time course of alpha 7nAChR expression following injury was assessed by immunohistochemistry and western blotting, and local inflammation, as indicated by the expression of tumor necrosis factor (TNF)-alpha, was detected by enzyme-linked immunosorbent assay. Axonal regeneration was evaluated by the pinch-test, morphometric analysis, and by measuring growth-associated protein 43 expressions. Local alpha 7nAChR expression increased on day 1, peaked on day 3, and remained elevated on day 5 following nerve injuries. Prominent alpha 7nAChR immunoreactivity was observed in Schwann cells, endothelial cells of the capillaries, and a small number of inflammatory cells. Application of the selective alpha 7nAChR agonist PNU-282987 decreased TNF-alpha level and enhanced axonal regeneration, but this effect was blocked by concomitant treatment with methyllycaconitine, a alpha 7nAChR antagonist. The results indicate that the local expression of alpha 7nAChR is increased during the early stages of sciatic nerve injury, and application of a alpha 7nAChR agonist promotes axonal regeneration by suppression of TNF-alpha-mediated inflammation. The alpha 7nAChR can act as a neuroprotective agent and alpha 7nAChR activation may be a useful therapeutic strategy to treat peripheral nerve injury.