Progesterone alleviates acute brain injury via reducing apoptosis and oxidative stress in a rat experimental subarachnoid hemorrhage model

• Progesterone significantly improved neurological deficits and reduced mortality.
• Progesterone inhibited cell apoptosis and reduced the expression of caspase-3.
• Progesterone significantly reduced the ratio of Bax/Bcl-2 and attenuated the release of cytochrome c from mitochondria.
• Progesterone induced antioxidative effects by elevating the activity of SOD and decreasing MDA content.

This study aimed to investigate the therapeutic effect of progesterone on acute brain injury after subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage was induced in male Sprague–Dawley rats (n = 72) by endovascular perforation. Progesterone (8 mg/kg or 16 mg/kg) was administered to rats at 1, 6, and 12 h after SAH. Mortality, neurologic deficits, cell apoptosis, expression of apoptotic markers, the level of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were assayed at 24 h after experimental SAH. Mortality, cell apoptosis and the expression of caspase-3 were decreased, and improved neurological function was observed in the progesterone-treated SAH rats. Further, exploration demonstrated that progesterone significantly reduced the ratio of Bax/Bcl-2 and attenuated the release of cytochrome c from mitochondria. Progesterone also induced anti-oxidative effects by elevating the activity of SOD and decreasing MDA content after SAH. Furthermore, dose-response relationships for progesterone treatment were observed, and high doses of progesterone enhanced the neuroprotective effects. Progesterone treatment could alleviate acute brain injury after SAH by inhibiting cell apoptosis and decreasing damage due to oxidative stress. The mechanism involved in the anti-apoptotic effect was related to the mitochondrial pathway. These results indicate that progesterone possesses the potential to be a novel therapeutic agent for the treatment of acute brain injury after SAH.