title: Apelin-13 protects the brain against ischemia/reperfusion injury through activating PI3K/Akt and ERK1/2 signaling pathways.
abstract: Apelin has been proved to protect the heart against ischemia/reperfusion (I/R) injury via the activation of phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) signaling pathways. Whether this protective effect applies to brain I/R injury needed to be explored. We therefore investigated the potential neuroprotective role of Apelin-13 and the underlying mechanisms. Focal transient cerebral I/R model in male ICR mice was induced by 60min of ischemia followed by reperfusion. Apelin-13 intracerebroventricular injection was performed 15 min before reperfusion. Neurological function, infarct volume, brain edema and apoptosis were measured at 24h after stroke. To further test the mechanism of Apelin-13, PI3K inhibitor LY294002 and ERK1/2 inhibitor PD98059 were injected into the lateral cerebral ventricle 15min before ischemia. Compared with the Vehicle group, Apelin-13 significantly ameliorated neurological deficit, infarct volume, brain edema and reduced TUNEL-positive cells. Bax, caspase-3 and cleaved caspase-3 were down-regulated and Bcl-2 up-regulated. While, the effect of Apelin-13 on Bax, Bcl-2, caspase-3 and cleaved caspase-3 was attenuated by LY294002 and PD98059. Apelin protected the brain against I/R insult injury, and this effect may be through activation of PI3K/Akt and ERK1/2 signaling pathways.
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei 050000, PR China. Electronic address: zhang6xj@heinfo.net.
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Cui
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Cong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Litao
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000473:pathology / Q000517:prevention & control; D020520:Brain Infarction / Q000473:pathology / Q000517:prevention & control; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D053148:Caspase 3 / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008813:Mice, Inbred ICR; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*; D015398:Signal Transduction
chemical_list: D053148:Caspase 3; D002867:Chromones; D005419:Flavonoids; D036341:Intercellular Signaling Peptides and Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D009025:Morpholines; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; C495199:apelin-13 peptide; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: Apelin-13; Cerebral ischemia/reperfusion; ERK1/2; PI3K/Akt