S-oxiracetam ameliorates ischemic stroke induced neuronal apoptosis through up-regulating α7 nAChR and PI3K / Akt / GSK3β signal pathway in rats

  • Neurochem Int. 2018 May;115:50-60. doi: 10.1016/j.neuint.2018.01.008.
Wenxiang Fan  1 ,  Xiang Li  1 ,  Liangliang Huang  1 ,  Shucheng He  1 ,  Zhicheng Xie  1 ,  Yuxin Fu  1 ,  Weirong Fang  2 ,  Yunman Li  3
Affiliations
  • 1. State Key Laboratory of Natural Medicines, Department of Physiology, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
  • 2. State Key Laboratory of Natural Medicines, Department of Physiology, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: [email protected].
  • 3. State Key Laboratory of Natural Medicines, Department of Physiology, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: [email protected].
PMID: 29355569 DOI: 10.1016/j.neuint.2018.01.008
Abstract

Ischemic stroke, the main reason for severe disabilities in the world, is associated with a high incidence of sensorimotor and cognitive dysfunction. In this study, we use the middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats and oxygen glucose deprivation/reoxygenation (OGD/R) model in fetal rat primary cortical neurons to investigate whether and how S-oxiracetam (S-ORC) protect brain injury from ischemic stroke. The results revealed that S-ORC reduced brain infarct size and lessened neurological dysfunction after stroke. Further study demonstrated that S-ORC diminished TUNEL positive cells, increased cell viability, decreased LDH activity, and inhibited cell apoptotic rate. Furthermore, S-ORC inhibited neuronal Apoptosis by activating the PI3K/Akt/GSK3β signaling pathway via α7 nAChR, which was evidenced by α7 nAChR siRNA. In conclusion, our findings strongly suggest that S-ORC could be used as an effective neuroprotective agent for ischemic stroke due to its effect in preventing neuronal Apoptosis.

Keywords
Apoptosis; GSK3β; Ischemic stroke; S-oxiracetam; α7 nAChR.
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