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. 2023 May 24;17:1191629. doi: 10.3389/fncel.2023.1191629

TABLE 2.

Therapeutic strategy by targeting mitochondrial dysfunctions to inhibit cerebral ischemia/reperfusion injury (CI/RI).

Cell deaths Interventions Model Subjects Mitochondrial associated targets Functions References
Pyroptosis Idebenone OGD/R and tMCAO PC12 cells, BV2 cells, and rat mtDNA and mtROS Idebenone suppresses activation of NLRP3 and ameliorates NLRP3-mediating damage in I/R. Peng et al., 2020
Medioresinol OGD, tMCAO bEnd.3 cells, BMVECs, and mice mtROS MDN decreases mtROS through PPARα/GOT1 axis and ameliorate the pyroptosis and ischemic brain injury. Wang Y. et al., 2021
Umbelliferone MCAO/R Rat ROS/TXNIP UMB protects focal cerebral ischemic through the inhibition of TXNIP/NLRP3 inflammasome and activation of PPAR-γ. Wang et al., 2015
Apoptosis miR-668 inhibitor tMCAO/R Rat Drp1, mtROS, Bax/Bcl-2 The miR-668 inhibitor prevents neuronal apoptosis in CI/RI by modulating mitochondrial function and regulating NLRP3 signaling. He and Zhang, 2020
Candesartan OGD/R PC12 cells Bax Candesartan inhibits apoptosis by downregulation of Bax and cleaved caspase-3 in OGD/R-PC12 cells. Ding et al., 2022
Edaravone dexborneol Four-vessel occlusion (4-VO) Rat Bax/Bcl-2 Edaravone-Dexborneol alleviates cerebral ischemic injury via reduction of apoptosis and neuron damage. Zhang W. et al., 2022
Tong-Qiao-Huo-Xue-Decoction formula MCAO Rat Bax/Bcl-2 TQHXD protects neurons from I/R damage and prevents apoptosis. Yuan et al., 2022
CsA BBCAO/R Rat Bax/Bcl-2 CsA decreases Bax/Bcl-2 ratio as well as caspase-3 activation. Fakharnia et al., 2017
Necroptosis CsA BBCAO/R Rat mPTP CsA inhibits mPTP opening and reduces RIP1 and RIP3 levels. Fakharnia et al., 2017
Infliximab tMCAO Rat Mitochondrial membrane potential Infliximab ameliorates endothelial necroptosis and reduces mitochondrial damage, cytoplasm transparency, and BBB permeability. Chen et al., 2019
rhTrx-1 MCAO C57BL/6 mice Mitochondrial membrane potential rhTrx-1 provides neuroprotection in IS-induced microglial neuroinflammation by inhibiting RIPK1 expression Jiao et al., 2020
Ferroptosis UBIAD1 MCAO/R, OGD/R Rat, primary neurons Mitochondrial protein complexes UBIAD1 modulates I/R-mediated ferroptosis by restoring mitochondrial dysfunctions and enhances antioxidative capacities. Huang et al., 2022
FtMt MCAO/R Mice FtMt FtMt protects against CI/RI-induced ferroptosis. Wang P. et al., 2021
Ferrostatin-1 t-BHP treatment PC12 cells Mitochondrial membrane potential, ATP production, and mtROS Ferrostatin-1 reverses ferroptosis-induced mitochondrial dysfunctions Wu C. et al., 2018