S-oxiracetam Facilitates Cognitive Restoration after Ischemic Stroke by Activating α7nAChR and the PI3K-Mediated Pathway.

Abstract

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.

• Authors: Wenxiang Fan, Ying Zhang, Xiaomin Li, Chi Xu
• Journal: Neurochemical research (Neurochem Res) Vol. 46 Issue 4 Pg. 888-904 (Apr 2021) ISSN: 1573-6903 [Electronic] United States
• PMID: 33481205 (Publication Type: Journal Article)

Chemical References

• Disks Large Homolog 4 Protein
• Dlg4 protein, rat
• Nootropic Agents
• Pyrrolidines
• Synaptophysin
• Syp protein, rat
• alpha7 Nicotinic Acetylcholine Receptor
• oxiracetam

Topics

• Animals
• CA1 Region, Hippocampal (drug effects, pathology)
• Cognitive Dysfunction (drug therapy, pathology)
• Disks Large Homolog 4 Protein (metabolism)
• Infarction, Middle Cerebral Artery (drug therapy, pathology)
• Ischemic Stroke (drug therapy, pathology)
• Male
• Morris Water Maze Test (drug effects)
• Nootropic Agents (therapeutic use)
• Phosphatidylinositol 3-Kinases (metabolism)
• Pyrrolidines (therapeutic use)
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Stereoisomerism
• Synaptophysin (metabolism)
• alpha7 Nicotinic Acetylcholine Receptor (metabolism)