Endothelin-1-induced focal cerebral ischemia in the growth hormone/IGF-1 deficient Lewis Dwarf rat.
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.
['Yan|Han|H|', 'Mitschelen|Matthew|M|', 'Toth|Peter|P|', 'Ashpole|Nicole M|NM|', 'Farley|Julie A|JA|', 'Hodges|Erik L|EL|', 'Warrington|Junie P|JP|', 'Han|Song|S|', 'Fung|Kar-Ming|KM|', 'Csiszar|Anna|A|', 'Ungvari|Zoltan|Z|', 'Sonntag|William E|WE|']
D000375:Aging D000818:Animals D001253:Astrocytes D001929:Brain Edema D002545:Brain Ischemia D002544:Cerebral Infarction D004195:Disease Models, Animal D004392:Dwarfism D019332:Endothelin-1 D005260:Female D013006:Growth Hormone D007334:Insulin-Like Growth Factor I D008297:Male D051381:Rats D011917:Rats, Inbred Lew D011922:Rats, Mutant Strains
Cerebral ischemia Endothelin-1. Insulin-like growth factor-1 Vascular aging