Effects of peroxynitrite in brain I/R. (A) In brain I/R, peroxynitrite produced during the reperfusion stage facilitates the recruitment of Drp1 via nitration to initiate PINK1/Parkin-mediated mitophagy, which may contribute to brain I/R injury [48]. (B) Another model of brain I/R is cerebral ischemia with delayed t-PA treatment, which facilitates the production of peroxynitrite. HMGB1 is activated by peroxynitrite and then upregulates the expression of MMP9 via TLR2, resulting in BBB disruption and HT [64,65]. HMGB1, high mobility group box 1 protein; TLR2, toll-like receptor 2; MMP 9, matrix metalloproteinase 9; TJ, tight junction; HT, hemorrhagic transformation; Drp1, dynamin-related protein 1; PINK, PTEN-induced kinase; BBB, blood brain barrier. Reproduced with permission from Translational Stroke Research, 2020, 11, 967–982. Copyright © 2022, Springer Science Bussiness Media, LLC, part of Springer Nature.