title: Astaxanthin alleviates early brain injury following subarachnoid hemorrhage in rats: possible involvement of Akt/bad signaling.
abstract: Apoptosis has been proven to play a crucial role in early brain injury pathogenesis and to represent a target for the treatment of subarachnoid hemorrhage (SAH). Previously, we demonstrated that astaxanthin (ATX) administration markedly reduced neuronal apoptosis in the early period after SAH. However, the underlying molecular mechanisms remain obscure. In the present study, we tried to investigate whether ATX administration is associated with the phosphatidylinositol 3-kinase-Akt (PI3K/Akt) pathway, which can play an important role in the signaling of apoptosis. Our results showed that post-SAH treatment with ATX could cause a significant increase of phosphorylated Akt and Bad levels, along with a significant decrease of cleaved caspase-3 levels in the cortex after SAH. In addition to the reduced neuronal apoptosis, treatment with ATX could also significantly reduce secondary brain injury characterized by neurological dysfunction, cerebral edema and blood-brain barrier disruption. In contrast, the PI3K/Akt inhibitor, LY294002, could partially reverse the neuroprotection of ATX in the early period after SAH by downregulating ATX-induced activation of Akt/Bad and upregulating cleaved caspase-3 levels. These results provided the evidence that ATX could attenuate apoptosis in a rat SAH model, potentially, in part, through modulating the Akt/Bad pathway.
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210000, Jiangsu, China. xiaoming20111386@163.com.
authors: Xiang-Sheng
authors: XS
authors: Zhang
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210000, Jiangsu, China. zhangxsp@163.com.
authors: Xin
authors: X
authors: Zhang
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210000, Jiangsu, China. njwuqi@gmail.com.
authors: Qi
authors: Q
authors: Wu
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210000, Jiangsu, China. lwxzlw@gmail.com.
authors: Wei
authors: W
authors: Li
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210000, Jiangsu, China. njzhangqingrong@aliyun.com.
authors: Qing-Rong
authors: QR
authors: Zhang
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210000, Jiangsu, China. wangcx02@163.com.
authors: Chun-Xi
authors: CX
authors: Wang
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210000, Jiangsu, China. xiaoming20111386@163.com.
authors: Xiao-Ming
authors: XM
authors: Zhou
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210000, Jiangsu, China. solihua@gmail.com.
authors: Hua
authors: H
authors: Li
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210000, Jiangsu, China. shijx52@hotmail.com.
authors: Ji-Xin
authors: JX
authors: Shi
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210000, Jiangsu, China. mlzhou1979@hotmail.com.
authors: Meng-Liang
authors: ML
authors: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D024341:Xanthophylls / Q000494:pharmacology; D051025:bcl-Associated Death Protein / Q000378:metabolism*
chemical_list: C494821:Bad protein, rat; D018696:Neuroprotective Agents; D024341:Xanthophylls; D051025:bcl-Associated Death Protein; C005948:astaxanthine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3