Cerebral ischemia is a major cause of morbidity and permanent disability. To date, no treatments for
cerebral ischemia/
reperfusion injury can be effectively administered beyond 4-6 h after the ischemic insult. Our study aimed to clarify the significance of
Sirt3 during acute
cerebral ischemia and explore Sirt3-targeted
therapy for ischemic
injuries. Upon establishing the
oxygen-
glucose deprivation/reperfusion (OGD/R) cell model, changes of
Sirt3 protein levels and the effects of
Sirt3 overexpression on primary hippocampal neurons were detected at indicated time points. Moreover, mitochondrial damage was observed in neurons upon OGD/R injury. The results showed that compared with the normoxia group,
Sirt3 protein was significantly decreased in hippocampal neurons exposed to 1 h of OGD followed by 12 h of reperfusion. In addition, the reduction of
Sirt3 protein levels contributed to OGD/R-induced neuronal
injuries, a higher ratio of neuronal apoptosis, and extensive production of
reactive oxygen species (ROS). However, all neuronal
injuries were partly rescued by
Sirt3 overexpression induced by lentivirus transfection. Mitochondrial morphologies were significantly impaired after OGD/R, but partly salvaged by
Sirt3 overexpression. We further explored whether pharmacologically activating
Sirt3 is protective for neurons, and found that treatment with
honokiol (a
Sirt3 agonist) after OGD exposure activated
Sirt3 during reperfusion and significantly alleviated OGD/R-induced neuronal
injuries. Because mitochondrial functions are essential for neuronal survival, the current results indicate that
Sirt3 may be an efficient target to suppress ischemic
injuries via maintenance of mitochondrial homeostasis. Our current findings shed light on a novel therapeutic strategy against subacute ischemic
injuries.