S-oxiracetam Facilitates Cognitive Restoration after Ischemic Stroke by Activating α7nAChR and the PI3K-Mediated Pathway.
S-oxiracetam (S-ORC), a nootropic drug, was used to protect against ischemic stroke by lessening the blood brain barrier dysfunction and inhibiting neuronal apoptosis. However, the potential effects of S-ORC in the recovery of cognitive functions after ischemic stroke and the underlying mechanisms remains unclear. In this study, middle cerebral artery occlusion/reperfusion (MCAO/R) in rats was used as the animal model. By using Y-maze test, Morris water maze, triphenyl tetrazolium chloride (TTC) staining, terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate (dUTp) nick end labeling (TUNEL) assay, hematoxylin and eosin, immunohistochemical staining and western blot to evaluate the protective effect of S-ORC on cognitive recovery, we were able to confirm that S-ORC ameliorated spatial learning impairment, tissue loss, and hippocampal neuronal apoptosis and injury induced by MCAO/R in rats. These cognitive effects were achieved by restoring the normal function of synaptophysin and increasing PSD95 expression in the hippocampus. Furthermore, we found that methyllycaconitine, the antagonist of α7 nicotinic acetylcholine receptor (α7nAChR), and LY294002, the inhibitor of phosphoinositide 3-kinase (PI3K), were able to block the cognitive effects of S-ORC after MCAO/R in rats. In conclusion, α7nAChR and PI3K are key molecules that mediated the signaling pathway leading to S-ORC-induced cognitive restoration after MCAO/R.
['Fan|Wenxiang|W|', 'Zhang|Ying|Y|', 'Li|Xiaomin|X|', 'Xu|Chi|C|http://orcid.org/0000-0001-5470-7376']
D000818:Animals D056547:CA1 Region, Hippocampal D060825:Cognitive Dysfunction D000076122:Disks Large Homolog 4 Protein D020244:Infarction, Middle Cerebral Artery D000083242:Ischemic Stroke D008297:Male D000084443:Morris Water Maze Test D018697:Nootropic Agents D019869:Phosphatidylinositol 3-Kinases D011759:Pyrrolidines D017207:Rats, Sprague-Dawley D015398:Signal Transduction D013237:Stereoisomerism D016708:Synaptophysin D064569:alpha7 Nicotinic Acetylcholine Receptor
S-oxiracetam Ischemic stroke α7nAChR Apoptosis Learning and memory