Rapamycin prevents cerebral stroke by modulating apoptosis and autophagy in penumbra in rats

Annals of Clinical and Translational Neurology
Meiling WuLing-Hui Zeng

Abstract

Whether activation or inhibition of the mTOR pathway is beneficial to ischemic injury remains controversial. It may result from the different reaction of ischemic penumbra and core to modulation of mTOR pathway after cerebral ischemia-reperfusion injury in rats. Longa's middle cerebral artery occlusion (MCAO) method was conducted to induce the focal cerebral ischemia-reperfusion. Western blot analysis was used to examine the protein expression involving mTOR pathway, apoptosis, and autophagy-related proteins. TTC staining and Fluoro-Jade B staining was conducted to detect the infarct volume and cell apoptosis, respectively. Neurological function was measured by modified neurological severity score and left-biased swing. mTOR signaling pathway was activated in ischemic penumbra and decreased in ischemic core after ischemia and ischemia-reperfusion. Ischemia-reperfusion injury induced the increase in cleaved caspase 9 and caspase 3 both in ischemic penumbra and in ischemic core, whereas the expression of phosphorylated ULK1, Beclin 1 and LC3-II was decreased. Rapamycin pre or postadministration inhibited the overactivation of mTOR pathway in ischemic penumbra. Ameliorated neurological function and reduced infarct volume were obse...Continue Reading

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Dec 19, 2018·Acta Pharmacologica Sinica·Yu-Ting LuJing-Ya Li
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