title: Akt Specific Activator SC79 Protects against Early Brain Injury following Subarachnoid Hemorrhage.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University , 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, P. R. China.
authors.forename: Dingding
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University , 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, P. R. China.
authors.forename: Huasheng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University , 22 Hankou Road, Nanjing 210093, Jiangsu Province, P. R. China.
authors.forename: Shuangying
authors.initials: S
authors.lastname: Hao
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University , 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, P. R. China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Second Military Medical University , Shanghai 200433, China.
authors.forename: Zihuan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui 230031, P. R. China.
authors.forename: Yangchun
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University , 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, P. R. China.
authors.forename: Zong
authors.initials: Z
authors.lastname: Zhuang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University , 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University , 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, P. R. China.
authors.forename: Mengliang
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University , 22 Hankou Road, Nanjing 210093, Jiangsu Province, P. R. China.
authors.forename: Kuanyu
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University , 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, P. R. China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Hang
mesh_terms: D000085:Acetates; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001578:Benzopyrans; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy*
chemical_list: C000614067:AKT activator SC79; D000085:Acetates; D000975:Antioxidants; D001578:Benzopyrans; D018696:Neuroprotective Agents
keywords: Akt; SC79; Subarachnoid hemorrhage; antiapoptosis; antioxidation; early brain injury