Protective effects of PGC-1α via the mitochondrial pathway in rat brains after intracerebral hemorrhage

Peroxisome-proliferator-activated receptor co-activator-1 alpha (PGC-1 alpha) is a transcriptional co-activator that coordinately regulates genes required for mitochondria] biogenesis, which stimulates mitochondrial activity. It is also a major factor in the up-regulation of antioxidant activities that are a response to oxidative stress. However, the role of PGC-1 alpha after intracerebral hemorrhage (ICH) has not been studied. The purpose of the present work was to investigate the effects and mechanism of PGC-1 alpha after ICH in the brain. Brain injury was induced by injecting autologous arterial blood (50 mu L) into the rat brain. PGC-1 alpha siRNAs were injected into rat brains 24 h prior to ICH. Then, 72 h after ICH, brains were collected for investigation. Post-assessment included western blot analysis, RT-PCR assay, neurobehavioral function testing, measurement of brain water content, high-performance liquid chromatography (HPLC), and projection electron microscopy on ICH rat models. The concentration of PGC-1 alpha was higher in the ipsilateral striatum after ICH, peaking around 72 h after ICH. The expression of NRF-1, TFAM, SOD2, UCP2, mitochondrial DNA, ATP concentration, mitochondrial quantity, and brain water content were increased 72 h after ICH. However, the neurological score was decreased 72 h after ICH. Treatment with PGC-1 alpha siRNAs significantly decreased the neurological score, ATP concentration, number of mitochondria, expression of NRF-1, TFAM, SOD2, UCP2, and mitochondria] DNA, and increased brain water content and formation of mitochondrial myelin layer structures. In conclusion, our data suggest that PGC-1 alpha protects rat brains via a mitochondrial pathway following ICH. Key words: PGC-1 alpha intracerebral hemorrhage (ICH); mitochondrial; neuroprotection. (C) 2016 Published by Elsevier B.V.