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

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

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=14

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2021.778569

DOI=10.3389/fnmol.2021.778569

ISSN=1662-5099

ABSTRACT=<p>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 <italic>in vivo</italic> studies) and the TOXRTOOL checklist (for <italic>in vitro</italic> 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 <italic>c</italic>, 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).</p><p><bold>Systematic Review Registration:</bold> [<ext-link ext-link-type="uri" xlink:href="https://www.crd.york.ac.uk/prospero/" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.crd.york.ac.uk/prospero/</ext-link>], identifier [CRD42020205808].</p>