Effects of Mdivi-1 on Neural Mitochondrial Dysfunction and Mitochondria-Mediated Apoptosis in Ischemia-Reperfusion Injury After Stroke: A Systematic Review of Preclinical Studies

Nguyen Thanh Nhu; Qing Li; Yijie Liu; Jian Xu; Shu-Yun Xiao; Shin-Da Lee

doi:10.3389/fnmol.2021.778569

Effects of Mdivi-1 on Neural Mitochondrial Dysfunction and Mitochondria-Mediated Apoptosis in Ischemia-Reperfusion Injury After Stroke: A Systematic Review of Preclinical Studies

Front Mol Neurosci. 2021 Dec 24:14:778569. doi: 10.3389/fnmol.2021.778569. eCollection 2021.

Authors

Nguyen Thanh Nhu¹, Qing Li², Yijie Liu³, Jian Xu⁴, Shu-Yun Xiao⁴, Shin-Da Lee^{5

6

7}

Affiliations

¹ Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho, Vietnam.
² Department of Rehabilitation, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
³ Institute of Rehabilitation Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
⁴ Department of Brain and Mental Disease, Shanghai Hospital of Traditional Chinese Medicine, Shanghai, China.
⁵ Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan.
⁶ Department of Physical Therapy, Asia University, Taichung, Taiwan.
⁷ School of Rehabilitation Medicine, Weifang Medical University, Weifang, China.

Abstract

This systematic review sought to determine the effects of Mitochondrial division inhibitor-1 (Mdivi-1) on neural mitochondrial dysfunction and neural mitochondria-mediated apoptosis in ischemia/reperfusion (I/R) injury after ischemic stroke. Pubmed, Web of Science, and EMBASE databases were searched through July 2021. The studies published in English language that mentioned the effects of Mdivi-1 on neural mitochondrial dysfunction and neural mitochondria-mediated apoptosis in I/R-induced brain injury were included. The CAMARADES checklist (for in vivo studies) and the TOXRTOOL checklist (for in vitro studies) were used for study quality evaluation. Twelve studies were included (median CAMARADES score = 6; TOXRTOOL scores ranging from 16 to 18). All studies investigated neural mitochondrial functions, providing that Mdivi-1 attenuated the mitochondrial membrane potential dissipation, ATP depletion, and complexes I-V abnormalities; enhanced mitochondrial biogenesis, as well as inactivated mitochondrial fission and mitophagy in I/R-induced brain injury. Ten studies analyzed neural mitochondria-mediated apoptosis, showing that Mdivi-1 decreased the levels of mitochondria-mediated proapoptotic factors (AIF, Bax, cytochrome c, caspase-9, and caspase-3) and enhanced the level of antiapoptotic factor (Bcl-2) against I/R-induced brain injury. The findings suggest that Mdivi-1 can protect neural mitochondrial functions, thereby attenuating neural mitochondria-mediated apoptosis in I/R-induced brain injury. Our review supports Mdivi-1 as a potential therapeutic compound to reduce brain damage in ischemic stroke (PROSPERO protocol registration ID: CRD42020205808). Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42020205808].

Keywords: Mdivi-1; apoptosis; ischemia-reperfusion injury; mitochondrial function; stroke.

Publication types

Review