Mitochondria-mediated oxidative stress and apoptosis lead greatly to early brain injuries (EBI) following subarachnoid hemorrhage (SAH). This research hypothesized that activation of melanocortin 1 receptor (MC1R), using BMS-470539, attenuates EBI by controlling mitochondrial metabolic process after SAH. Methods: We utilized BMS-470539, MSG-606, selisistat, and PGC-1α to ensure the neuroprotective results of MC1R. We evaluated short- and lengthy-term neurobehavior after SAH. Western blotting, immunofluorescence, and Golgi staining techniques were performed to evaluate alterations in protein levels. Results: The outcomes of western blotting recommended the expression of SIRT1 and PGC-1α were elevated, reaching their peaks at 24 h following SAH. Furthermore, BMS-470539 treatment particularly attenuated nerve deficits, as well as reduced lengthy-term spatial learning and memory impairments brought on by SAH. The actual neuroprotective mechanisms from the BMS-470539/MC1R system were mediated with the suppression of oxidative stress, apoptosis, and mitochondrial fission by growing the amount of SIRT1, PGC-1α, UCP2, SOD, GPx, Bcl-2, cyto-Drp1, and ATP, while reducing the amounts of cleaved caspase-3, Bax, mito-Drp1, ROS, GSH/GSSG, and NADPH/NADP ratios. The neuroprotective results of the BMS-470539/MC1R system were considerably abolished by MSG-606, selisistat, and PGC-1α siRNA. Conclusions: The activation of MC1R with BMS-470539 considerably attenuated EBI after SAH by suppressing the oxidative stress, apoptosis, and mitochondrial fission with the AMPK/SIRT1/PGC-1α signaling path.

Leave a Reply

Your email address will not be published. Required fields are marked *


You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>