title: The anti-inflammatory and neuroprotective effects of ghrelin in subarachnoid hemorrhage-induced oxidative brain damage in rats.
abstract: To elucidate the putative neuroprotective effects of ghrelin in subarachnoid hemorrhage (SAH)-induced brain injury, Wistar albino rats (n = 54) were divided into sham-operated control, saline-treated SAH, and ghrelin-treated (10 microg/kg/d IP) SAH groups. The rats were injected with blood (0.3 mL) into the cisterna magna to induce SAH, and were sacrificed 48 h after the neurological examination scores were recorded. In plasma samples, neuron-specific enolase (NSE), S-100beta protein, TNF-alpha, and IL-1beta levels were evaluated, while forebrain tissue samples were taken for the measurement of malondialdehyde (MDA), glutathione (GSH), reactive oxygen species levels, myeloperoxidase (MPO), Na(+)-K(+)-ATPase activity, and DNA fragmentation ratio. Brain tissue samples containing the basilar arteries were obtained for histological examination, while cerebrum and cerebellum were removed for the measurement of blood-brain barrier (BBB) permeability and brain water content. The neurological scores were impaired at 48 h after SAH induction, and SAH caused significant decreases in brain GSH content and Na(+)-K(+)-ATPase activity, and increases in chemiluminescence, MDA levels, and MPO activity. Compared with the control group, the protein levels of NSE, S-100beta, TNF-alpha, and IL-1beta in plasma were also increased, while ghrelin treatment prevented all SAH-induced alterations observed both biochemically and histopathologically. The results demonstrate that ghrelin alleviates SAH-induced oxidative brain damage, and exerts neuroprotection by maintaining a balance in oxidant-antioxidant status, by inhibiting proinflammatory mediators, and preventing the depletion of endogenous antioxidants evoked by SAH.
authors.affiliation: Haydarpasa Numune Education and Research Hospital, Department of Neurosurgery, Istanbul, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Erşahin
authors.forename: Hale Z
authors.initials: HZ
authors.lastname: Toklu
authors.forename: Can
authors.initials: C
authors.lastname: Erzik
authors.forename: Sule
authors.initials: S
authors.lastname: Cetinel
authors.forename: Dilek
authors.initials: D
authors.lastname: Akakin
authors.forename: Ayliz
authors.initials: A
authors.lastname: Velioğlu-Oğünç
authors.forename: Sermin
authors.initials: S
authors.lastname: Tetik
authors.forename: Zarife N
authors.initials: ZN
authors.lastname: Ozdemir
authors.forename: Göksel
authors.initials: G
authors.lastname: Sener
authors.forename: Berrak C
authors.initials: BC
authors.lastname: Yeğen
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D053938:DNA Fragmentation; D004797:Enzyme-Linked Immunosorbent Assay; D054439:Ghrelin / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D053583:Interleukin-1beta / Q000097:blood; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009281:Naphthalenes; D009414:Nerve Growth Factors / Q000097:blood; D018696:Neuroprotective Agents / Q000494:pharmacology; D010082:Oxepins; D010751:Phosphopyruvate Hydratase / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C461941:1-phenyl-1,4-epoxy-1H,4H-naphtho(1,8-de)(1,2)dioxepin; D054439:Ghrelin; D053583:Interleukin-1beta; D009281:Naphthalenes; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D010082:Oxepins; D017382:Reactive Oxygen Species; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D014409:Tumor Necrosis Factor-alpha; D010751:Phosphopyruvate Hydratase