title: Endogenous ghrelin's role in hippocampal neuroprotection after global cerebral ischemia: does endogenous ghrelin protect against global stroke?
abstract: Ghrelin is a gastrointestinal hormone with a well-characterized role in feeding and metabolism. Recent evidence suggests that ghrelin may also be neuroprotective after injury in animal models of cerebral ischemia. Thus exogenous ghrelin treatment can improve cell survival, reduce infarct size, and rescue memory deficits in focal ischemia models, doing so by suppressing inflammation and apoptosis. Endogenous ghrelin plays a key a role in a number of physiological processes, including feeding, metabolism, stress, and anxiety. However, no study has examined whether endogenous ghrelin also contributes to neuroprotection after cerebral ischemia. Here, we aimed to determine whether endogenous ghrelin normally protects against neuronal cell death and cognitive impairments after global cerebral ischemia and whether such changes are linked with inflammation or apoptosis. We used a two-vessel occlusion (2VO) model of global cerebral ischemia in wild-type (wt) and ghrelin knockout (ghr-/-) C57/Bl6J mice. ghr-/- mice had improved cell survival in the Cornu Ammonis(CA)-2/3 region of the hippocampus-a region of significant growth hormone secretagogue receptor expression. They also displayed less cellular degeneration than wt mice after the 2VO (Fluoro-Jade) and had less cognitive impairment in the novel object-recognition test. These outcomes were despite evidence of more neuroinflammation and apoptosis in the ghr-/- and less of a postsurgery hypothermia. Finally, we found that mortality in the week following the 2VO was reduced more in ghr-/- mice than in wt. Overall, these experiments point to a neurodegenerative but antiapoptotic effect of endogenous ghrelin in this model of global ischemia, highlighting that further research is essential before we can apply ghrelin treatments to neurodegenerative insults in the clinic.
authors.affiliation: School of Health Sciences and Health Innovations Research Institute, Royal Melbourne Institute of Technology University, Melbourne, Victoria, Australia.
authors.forename: Rachel
authors.initials: R
authors.lastname: Kenny
authors.forename: Guohui
authors.initials: G
authors.lastname: Cai
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Bayliss
authors.forename: Melanie
authors.initials: M
authors.lastname: Clarke
authors.forename: Yuen Ling
authors.initials: YL
authors.lastname: Choo
authors.forename: Alyson A
authors.initials: AA
authors.lastname: Miller
authors.forename: Zane B
authors.initials: ZB
authors.lastname: Andrews
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Spencer
mesh_terms: D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000473:pathology; D001522:Behavior, Animal / Q000502:physiology; D002545:Brain Ischemia / Q000235:genetics / Q000473:pathology*; D056651:CA2 Region, Hippocampal / Q000473:pathology; D056654:CA3 Region, Hippocampal / Q000473:pathology; D003071:Cognition / Q000502:physiology; D017931:DNA Primers; D004660:Encephalitis / Q000473:pathology; D054439:Ghrelin / Q000235:genetics / Q000502:physiology*; D006624:Hippocampus / Q000473:pathology*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000502:physiology; D009474:Neurons / Q000473:pathology; D011597:Psychomotor Performance / Q000502:physiology; D054440:Receptors, Ghrelin / Q000502:physiology; D021641:Recognition, Psychology / Q000502:physiology; D020521:Stroke / Q000235:genetics / Q000473:pathology*
chemical_list: D017931:DNA Primers; D054439:Ghrelin; D054440:Receptors, Ghrelin
keywords: ghrelin; ghrelin knockout; neurodegeneration; stroke; two-vessel occlusion