title: Endothelin-1-induced focal cerebral ischemia in the growth hormone/IGF-1 deficient Lewis Dwarf rat.
abstract: Aging is a major risk factor for cerebrovascular disease. Growth hormone (GH) and its anabolic mediator, insulin-like growth factor (IGF)-1, decrease with advancing age and this decline has been shown to promote vascular dysfunction. In addition, lower GH/IGF-1 levels are associated with higher stroke mortality in humans. These results suggest that decreased GH/IGF-1 level is an important factor in increased risk of cerebrovascular diseases. This study was designed to assess whether GH/IGF-1-deficiency influences the outcome of cerebral ischemia. We found that endothelin-1-induced middle cerebral artery occlusion resulted in a modest but nonsignificant decrease in cerebral infarct size in GH/IGF-1 deficient dw/dw rats compared with control heterozygous littermates and dw/dw rats with early-life GH treatment. Expression of endothelin receptors and endothelin-1-induced constriction of the middle cerebral arteries were similar in the three experimental groups. Interestingly, dw/dw rats exhibited reduced brain edema and less astrocytic infiltration compared with their heterozygous littermates and this effect was reversed by GH-treatment. Because reactive astrocytes are critical for the regulation of poststroke inflammatory processes, maintenance of the blood-brain barrier and neural repair, further studies are warranted to determine the long-term functional consequences of decreased astrocytic activation in GH/IGF-1 deficient animals after cerebral ischemia.
authors.affiliation: Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City.
authors.forename: Han
authors.initials: H
authors.lastname: Yan
authors.affiliation: Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City.
authors.forename: Matthew
authors.initials: M
authors.lastname: Mitschelen
authors.affiliation: Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City.
authors.forename: Peter
authors.initials: P
authors.lastname: Toth
authors.affiliation: Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Ashpole
authors.affiliation: Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Farley
authors.affiliation: Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City.
authors.forename: Erik L
authors.initials: EL
authors.lastname: Hodges
authors.affiliation: Present address: Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson, MS 39216.
authors.forename: Junie P
authors.initials: JP
authors.lastname: Warrington
authors.affiliation: Present address: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065.
authors.forename: Song
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City.
authors.forename: Kar-Ming
authors.initials: KM
authors.lastname: Fung
authors.affiliation: Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City.
authors.forename: Anna
authors.initials: A
authors.lastname: Csiszar
authors.affiliation: Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Ungvari
authors.affiliation: Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City. william-sonntag@ouhsc.edu.
authors.forename: William E
authors.initials: WE
authors.lastname: Sonntag
mesh_terms: D000375:Aging / Q000473:pathology* / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology; D001929:Brain Edema / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004392:Dwarfism / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D019332:Endothelin-1 / Q000502:physiology*; D005260:Female; D013006:Growth Hormone / Q000172:deficiency* / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000172:deficiency* / Q000502:physiology; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011922:Rats, Mutant Strains
chemical_list: D019332:Endothelin-1; C548904:insulin-like growth factor-1, rat; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone
keywords: Cerebral ischemia; Endothelin-1.; Insulin-like growth factor-1; Vascular aging
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