Open Access

ARTICLE

Spontaneous running wheel improves neuroprotection efficacy of ischemic postconditioning in mice following ischemia/reperfusion injury

Hong YE^1,6,#, WeiWei Wang^2,#, Yu Ding^3,#, XiaoLei Liu^4,#, WenJI Jia¹, WeiLi Luo¹, HuiJuan Fan¹, HongQun Zhou¹, Jin Wang¹, JianLong Ju¹, DongMing Zhou⁷, TianHao Bao^5,1,*, YuHong Zhu^1,*

1 Department of Neurology, the Second Affiliated Hospital of Kunming Medical University, Kunming, China
2 Department of Cardiology, the Second Affiliated Hospital of Kunming Medical University, Kunming, China
3 Department of Ultrasound, the Second Affiliated Hospital of Kunming Medical University, Kunming, China
4 Department of Neurology, the First Affiliated Hospital of Kunming Medical University, Kunming, China
5 The Mental Health Center of Kunming Medical University, Kunming, China
6 Kunming Medical University, Kunming, China
7 Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada
# Hong Ye, Yu Ding, WeiWei Wang, XiaoLei Liu contributed equally to this article.

^* Address correspondence to: TianHao Bao, ; YuHong Zhu,

BIOCELL 2018, 42(3), 79-86. https://doi.org/10.32604/biocell.2018.04615

Abstract

Ischemic postconditioning (IP) has been shown to provide protection for ischemia/reperfusion (IR) injury, but its efficacy is limited. In this study we hypothesized that spontaneous running wheel (RW) could improve neuroprotection efficacy of IP for IR. We established mouse models of IR and showed that compared to Sham group, IR group had obvious brain infract and neurological dysfunction. In IR+IP group, brain infract and neurological dysfunction improved compared to IR group. However, in IR+IP+RW group brain infract and neurological dysfunction improved much better. TUNEL assay showed that IP but not RW significantly reduced the number of apoptotic cells after IR. However, the number of apoptotic cells was significantly reduced in RW+IP group. In addition, the levels of pro-apoptotic factors increased in IR group but significantly reduced in IR+IP+RW group, while the levels of antiapoptotic factors decreased in IR group but significantly increased in IR+IP+RW group. Moreover, in IR+IP+RW group, MDA level was further decreased and SOD level was further increased compared to IR+IP group. Finally, both PI3K inhibitor and STAT3 inhibitor significantly worsened brain infract and neurological dysfunction and promoted apoptosis in IR mice. In conclusion, RW combined with IP reduces brain infract and neurological dysfunction in mice after IR, and this is associated with enhanced anti-apoptotic and anti-oxidant benefits via the activation of PI3K and STAT3 pathways.

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