Abstract
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) has been shown to play a pivotal role in the regulation of mitochondrial biogenesis in diseases. Resveratrol (RSV), a natural polyphenolic reagent, has powerful antioxidant properties and the ability to scavenge mitochondrial reactive oxygen species (ROS) in a variety of central nervous system diseases. However, the underlying molecular mechanisms of RSV on mitochondrial biogenesis in early brain injury (EBI) following subarachnoid hemorrhage (SAH) remain poorly understood. This study aimed to explore the potential neuroprotective effects of RSV on mitochondrial biogenesis and function by activation of the PGC-1α signaling pathway in a prechiasmatic cistern SAH model. PGC-1α expression and related mitochondrial biogenesis were detected. Amounts of nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) were determined to evaluate the extent of mitochondrial biogenesis. Increased PGC-1α and mitochondrial biogenesis after SAH were observed in the temporal cortex. Resveratrol increased the expression of PGC-1α, NRF1, and TFAM, and promoted PGC-1α nuclear translocation. Moreover, RSV could scavenge excess ROS, increase the activity of superoxide dismutase (SOD), enhance the potential of mitochondrial membrane and ATP levels, reduce the number of mitochondrial DNA copy, and decrease the level of malondialdehyde (MDA). RSV significantly ameliorated the release of apoptosis-related cytokines, namely P53, cleaved caspase-3, cytochrome c, and BAX, leading to the amelioration of neuronal apoptosis, brain edema, and neurological impairment 24 h after SAH. These results indicate that resveratrol promotes mitochondrial biogenesis and function by activation of the PGC-1α signaling pathway in EBI following SAH.
Highlights
Subarachnoid hemorrhage (SAH) is a fatal cerebrovascular disease with high rates of morbidity and mortality
The findings presented above indicated that RSV improved mitochondrial biogenesis in early brain injury (EBI) following SAH
These findings indicated for the first time that RSV could promote mitochondrial biogenesis and function against SAHinduced oxidative stress and apoptosis via activation of the PGC-1α pathway
Summary
Subarachnoid hemorrhage (SAH) is a fatal cerebrovascular disease with high rates of morbidity and mortality. Accumulating evidence indicates that early brain injury (EBI) is the major cause of deterioration in patients with SAH. Treatment of EBI has been believed to be the principal target for patients with the disease. Studies have indicated that numerous pathophysiological processes are involved in the pathogenesis of EBI, such as mitochondrial dysfunction, oxidative stress, apoptosis, inflammation, autophagy, and brain edema (Fujii et al, 2013). Mitochondrial dysfunction plays a pivotal role in EBI.
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