title: Ghrelin alleviates early brain injury after subarachnoid hemorrhage via the PI3K/Akt signaling pathway.
abstract: Early brain injury (EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage (SAH). Although the neuroprotective effects of ghrelin have been demonstrated in several studies, whether ghrelin reduces EBI after SAH remains unknown. In this study, we hypothesized that treatment with ghrelin would attenuate EBI after SAH, and that this protection would be mediated, at least in part, by activation of the PI3K/Akt signaling pathway. Adult male Sprague-Dawley rats (n=100) were randomly divided into the following groups: control group (n=20), SAH group (n=20), SAH+vehicle group (n=20), SAH+ghrelin group (n=20) and SAH+ghrelin+LY294002 group (n=20). The rats were injected with autologous blood (0.3mL) into the prechiasmatic cistern to induce SAH. Ghrelin (80μg/kg, IP), or an equal volume of vehicle, was administered immediately after surgery. The PI3K inhibitor, LY294002, was applied to manipulate the proposed pathway. Mortality, neurological scores, brain edema, cell apoptosis, and the expression of p-Akt, and cleaved caspase-3 proteins were assayed after 24h SAH. Ghrelin significantly improved neurological function and reduced neuronal apoptosis and brain edema at 24h after SAH. The level of p-Akt, expressed mainly in neurons, was markedly up-regulated. Additionally, the level of cleaved caspase-3 was decreased by ghrelin treatment. The beneficial effects of ghrelin in SAH rats were partially suppressed by LY294002. These results demonstrate that ghrelin may reduce EBI after SAH, via a mechanism involving the PI3K/Akt signaling pathway.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Second Military Medical University, Shanghai, China.
authors.forename: Xiao-Ke
authors.initials: XK
authors.lastname: Hao
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Second Military Medical University, Shanghai, China; Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Chun-Xi
authors.initials: CX
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Guang-Bin
authors.initials: GB
authors.lastname: Xie
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Second Military Medical University, Shanghai, China.
authors.forename: He-Ming
authors.initials: HM
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, School of Medicine, Southern Medical University (Guangzhou), Jinling Hospital, Nanjing, Jiangsu Province, China.
authors.forename: Li-Tian
authors.initials: LT
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Meng-Liang
authors.initials: ML
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Second Military Medical University, Shanghai, China; Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Hang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Second Military Medical University, Shanghai, China; Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Ji-Xin
authors.initials: JX
authors.lastname: Shi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001925:Brain Damage, Chronic / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D001929:Brain Edema / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D053148:Caspase 3 / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D054439:Ghrelin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009460:Neurologic Examination; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D016037:Single-Blind Method; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D053148:Caspase 3; D002867:Chromones; D054439:Ghrelin; D009025:Morpholines; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494920:Akt1 protein, rat
keywords: Early brain injury; Ghrelin; PI3K/Akt; Subarachnoid hemorrhage