title: Axonal regeneration in early stages of sciatic nerve crush injury is enhanced by α7nAChR in rats.
abstract: This study investigated the role of alpha 7 nicotinic acetylcholine receptor (α7nAChR) in axonal regeneration after crush injury to the rat sciatic nerve. The time course of α7nAChR expression following injury was assessed by immunohistochemistry and western blotting, and local inflammation, as indicated by the expression of tumor necrosis factor (TNF)-α, 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 α7nAChR expression increased on day 1, peaked on day 3, and remained elevated on day 5 following nerve injuries. Prominent α7nAChR immunoreactivity was observed in Schwann cells, endothelial cells of the capillaries, and a small number of inflammatory cells. Application of the selective α7nAChR agonist PNU-282987 decreased TNF-α level and enhanced axonal regeneration, but this effect was blocked by concomitant treatment with methyllycaconitine, a α7nAChR antagonist. The results indicate that the local expression of α7nAChR is increased during the early stages of sciatic nerve injury, and application of a α7nAChR agonist promotes axonal regeneration by suppression of TNF-α-mediated inflammation. The α7nAChR can act as a neuroprotective agent and α7nAChR activation may be a useful therapeutic strategy to treat peripheral nerve injury.
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China.
authors.forename: Dewei
authors.initials: D
authors.lastname: Wang
authors.forename: Xuming
authors.initials: X
authors.lastname: Wang
authors.forename: Shuo
authors.initials: S
authors.lastname: Geng
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Bi
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D001549:Benzamides / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D015870:Gene Expression; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects; D018722:Nicotinic Agonists / Q000494:pharmacology; D051381:Rats; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists / Q000235:genetics / Q000378:metabolism*
chemical_list: D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D018722:Nicotinic Agonists; C498513:PNU-282987; D064569:alpha7 Nicotinic Acetylcholine Receptor