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CD4 T cell deficiency attenuates ischemic stroke, inhibits oxidative stress, and enhances Akt/mTOR survival signaling pathways in mice.


ABSTRACT: Background:Inhibition of CD4 T cells reduces stroke-induced infarction by inhibiting neuroinflammation in the ischemic brain in experimental stroke. Nevertheless, little is known about its effects on neuronal survival signaling pathways. In this study, we investigated the effects of CD4 T cell deficits on oxidative stress and on the Akt/mTOR cell signaling pathways after ischemic stroke in mice. Methods:MHC II gene knockout C57/BL6 mice, with significantly decreased CD4 T cells, were used. Stroke was induced by 60-min middle cerebral artery (MCA) occlusion. Ischemic brain tissues were harvested for Western blotting. Results:The impairment of CD4 T cell production resulted in smaller infarction. The Western blot results showed that iNOS protein levels robustly increased at 5 h and 24 h and then returned toward baseline at 48 h in wild-type mice after stroke, and gene KO inhibited iNOS at 5 h and 24 h. In contrast, the anti-inflammatory marker, arginase I, was found increased after stroke in WT mice, which was further enhanced in the KO mice. In addition, stroke resulted in increased phosphorylated PTEN, Akt, PRAS40, P70S6, and S6 protein levels in WT mice, which were further enhanced in the animals whose CD4 T cells were impaired. Conclusion:The impairment of CD4 T cell products prevents ischemic brain injury, inhibits inflammatory signals, and enhances the Akt/mTOR cell survival signaling pathways.

SUBMITTER: Zhang H 

PROVIDER: S-EPMC7398241 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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CD4 T cell deficiency attenuates ischemic stroke, inhibits oxidative stress, and enhances Akt/mTOR survival signaling pathways in mice.

Zhang Hongfei H   Xiong Xiaoxing X   Gu Lijuan L   Xie Weiying W   Zhao Heng H  

Chinese neurosurgical journal 20181108


<h4>Background</h4>Inhibition of CD4 T cells reduces stroke-induced infarction by inhibiting neuroinflammation in the ischemic brain in experimental stroke. Nevertheless, little is known about its effects on neuronal survival signaling pathways. In this study, we investigated the effects of CD4 T cell deficits on oxidative stress and on the Akt/mTOR cell signaling pathways after ischemic stroke in mice.<h4>Methods</h4>MHC II gene knockout C57/BL6 mice, with significantly decreased CD4 T cells, w  ...[more]

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