title: Progesterone alleviates acute brain injury via reducing apoptosis and oxidative stress in a rat experimental subarachnoid hemorrhage model.
abstract: 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 12h 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 24h 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.
authors.affiliation: Neurosurgerical Intensive Care Unit, The Second Affiliated Hospital of Zhejiang University School of Medicine, NO.88 Jiefang Road, Hangzhou 310009, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, NO.88 Jiefang Road, Hangzhou 310009, China.
authors.forename: Shenglong
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, NO.88 Jiefang Road, Hangzhou 310009, China.
authors.forename: Jingyin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, NO.88 Jiefang Road, Hangzhou 310009, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, NO.88 Jiefang Road, Hangzhou 310009, China.
authors.forename: Gao
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Clinical Medicine, Zhejiang Medical College, No.481 Binwen Road, Hangzhou 310053, China. Electronic address: yuying_dai@163.com.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Dai
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects*; D011374:Progesterone / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D011374:Progesterone; D008315:Malondialdehyde; D013482:Superoxide Dismutase
keywords: Acute brain injury; Apoptosis; Oxidative stress; Progesterone; Subarachnoid hemorrhage