Endothelin-1-Induced Focal Cerebral Ischemia in the Growth Hormone/IGF-1 Deficient Lewis Dwarf Rat
Year: 2014
Type: article
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.
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Ellison Medical Foundation, American Heart Association, Oklahoma Center for the Advancement of Science and Technology, National Institutes of Health, National Institute on Aging, National Center for Complementary and Alternative Medicine, National Center for Complementary and Integrative Health
Awards: G1583363307, G1714969075, G1860275249, G1897816485, Role of SIRT1 in vasoprotection, G2198435285, G2581117139, G3139818032, Microvascular mechanisms of neuroinflammation: role of Nrf2, G3272170628, G4542208516, G5450034612, G6843436329, G7262208464, G760902603, Vasoprotection by Caloric Restriction Mimetics in Aging, G8089820785, G8229779574, G8402183953, G86302415, NOVEL APPROACHES FOR REGULATION OF IGF-1 LEVELS THROUGHOUT THE LIFESPAN
OpenAlex ID: W2046689692