Effects of Mexidol on cerebral mitochondrial biogenesis following acute cerebrovascular events

Objective. To evaluate the effect of Mexidol on cerebral mitochondrial biogenesis during middle cerebral artery (MCA) occlusion-reperfusion. Material and methods. Male Wistar rats were used in this study. Focal cerebral ischemia was induced by endovascular occlusion-reperfusion of the right MCA following J. Koizumi’s method (1986), with an occlusion period of 60 minutes. At reperfusion onset, animals received a single intravenous injection of either saline or ethylmethylhydroxypyridine succinate (Mexidol) at 50 mg/kg. Relative levels of mitochondrial respiratory chain enzymes and regulatory transcription factors in the ischemic hemisphere were measured at 4, 8, and 24 hours post-reperfusion using Western blot analysis. Results. MCA occlusion-reperfusion did not affect the levels of the transcription factors Nrf1 and TFAM or the proteins NDUFV2, SDHA, MT-CYB, and COX2 in the ischemic hemisphere. However, PGC-1α and ATP5A1 were significantly reduced (p<0.05). Mexidol administration 4 hours after ischemia induction increased PGC-1α and ATP5A1 at 8 hours, as well as PGC-1α, NDUFV2, SDHA, and ATP5A1. At 24 hours, Nrf1, TFAM, PGC-1α, SDHA, and ATP5A1 levels were significantly elevated (p<0.05) compared with the control group. Conclusions. Single intravenous administration of Mexidol at 50 mg/kg at reperfusion onset following 60-minute MCA occlusion in rats is associated with increased levels of PGC-1α, TFAM, Nrf1, NDUFV2, SDHA, and ATP5A1 in the ischemic region. These findings support the hypothesis that Mexidol modulates mitochondrial biogenesis markers.