title: Protective Effect of Aliskiren in Experimental Ischemic Stroke: Up-Regulated p-PI3K, p-AKT, Bcl-2 Expression, Attenuated Bax Expression.
abstract: Aliskiren (ALK), a pharmacological renin inhibitor, is an effective antihypertensive drug and has potent anti-apoptotic activity, but it is currently unknown whether ALK is able to attenuate brain damage caused by acute cerebral ischemia independent of its blood pressure-lowering effects. This study aimed to investigate the role of ALK and its potential mechanism in cerebral ischemia. C57/BL6 mice were subjected to transient middle cerebral artery occlusion (tMCAO) and treated for 5 days with Vehicle or ALK (10 or 25 mg/kg per day via intragastric administration), whereas Sham-operated animals served as controls. Treatment with ALK significantly improved neurological deficits, infarct volume, brain water content and Nissl bodies after stroke (P < 0.05), which did not affect systemic blood pressure. Furthermore, the protection of ALK was also related to decreased levels of apoptosis in mice by enhanced activation of phosphatidylinositol 3-kinase (PI3K)/AKT pathway, increased level of Bcl-2 and reduced Bax expression (P < 0.05). In addition, ALK's effects were reversed by PI3K inhibitors LY294002 (P < 0.05). Our data indicated that ALK protected the brain from reperfusion injuries without affecting blood pressure, and this effect may be through PI3K/AKT signaling pathway.
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, People's Republic of China.|Hebei Key Laboratory for Neurology, Shijiazhuang, 050000, Hebei, People's Republic of China.|Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, 050000, Hebei, People's Republic of China.
authors.forename: Jiangyong
authors.initials: J
authors.lastname: Miao
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, People's Republic of China.|Hebei Key Laboratory for Neurology, Shijiazhuang, 050000, Hebei, People's Republic of China.|Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, 050000, Hebei, People's Republic of China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, People's Republic of China. zhang6xj@aliyun.com.|Hebei Key Laboratory for Neurology, Shijiazhuang, 050000, Hebei, People's Republic of China. zhang6xj@aliyun.com.|Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, 050000, Hebei, People's Republic of China. zhang6xj@aliyun.com.
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, People's Republic of China.|Hebei Key Laboratory for Neurology, Shijiazhuang, 050000, Hebei, People's Republic of China.|Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, 050000, Hebei, People's Republic of China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, People's Republic of China.|Hebei Key Laboratory for Neurology, Shijiazhuang, 050000, Hebei, People's Republic of China.|Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, 050000, Hebei, People's Republic of China.
authors.forename: Lili
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, People's Republic of China.|Hebei Key Laboratory for Neurology, Shijiazhuang, 050000, Hebei, People's Republic of China.|Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, 050000, Hebei, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ji
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, People's Republic of China.|Hebei Key Laboratory for Neurology, Shijiazhuang, 050000, Hebei, People's Republic of China.|Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, 050000, Hebei, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, 050000, Hebei, People's Republic of China. wangxl2014@yahoo.com.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Wang
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000517:prevention & control*; D005650:Fumarates / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020521:Stroke / Q000517:prevention & control; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D000577:Amides; C494827:Bax protein, mouse; D005650:Fumarates; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C446481:aliskiren; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: Aliskiren; Apoptosis; Cerebral ischemia; Neuroprotection