Akt Specific Activator SC79 Protects against Early Brain Injury following Subarachnoid Hemorrhage

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• 作者：Dingding Zhang ; Huasheng Zhang ; Shuangying Hao ; Huiying Yan ; Zihuan Zhang ; Yangchun Hu ; Zong Zhuang ; Wei Li ; Mengliang Zhou ; Kuanyu Li ; Chunhua Hang
• 刊名：ACS Chemical Neuroscience
• 出版年：2016
• 出版时间：June 15, 2016
• 年：2016
• 卷：7
• 期：6
• 页码：710-718
• 全文大小：651K
• 年卷期：0
• ISSN：1948-7193

文摘

A growing body of evidence demonstrates that Akt may serve as a therapeutic target for treatment of early brain injury following subarachnoid hemorrhage (SAH). The purpose of the current study was to evaluate the neuroprotective effect of Akt specific activator SC79 in an experimental rat model of SAH. SAH was induced by injecting 300 μL of blood into the prechiasmatic cistern. Intracerebroventricular (ICV) injection of SC79 (30 min post-SAH) induced the p-Akt (Ser473) expression in a dose-dependent manner. A single ICV dose treatment of SC79 (100 μg/rat) significantly increased the expression of Bcl-2 and p-GSK-3β (Ser9), decreased the protein levels of Bax, cytoplasm cytochrome c, and cleaved caspase-3, indicating the antiapoptotic effect of SC79. As a result, the number of apoptotic cells was reduced 24 h post SAH. Moreover, SC79 treatment alleviated SAH-induced oxidative stress, restored mitochondrial morphology, and improved neurological deficits. Strikingly, treatment of SC79 provided a beneficial outcome against neurologic deficit with a therapeutic window of at least 4 h post SAH by ICV injection and 30 min post SAH by intraperitoneal injection. Collectively, SC79 exerts its neuroprotective effect likely through the dual activities of antioxidation and antiapoptosis. These data provide a basic platform to consider SC79 as a novel therapeutic agent for treatment of SAH.