title: SOD1 overexpression prevents acute hyperglycemia-induced cerebral myogenic dysfunction: relevance to contralateral hemisphere and stroke outcomes.
abstract: Admission hyperglycemia (HG) amplifies vascular injury and neurological deficits in acute ischemic stroke, but the mechanisms remain controversial. We recently reported that ischemia-reperfusion (I/R) injury impairs the myogenic response in both hemispheres via increased nitration. However, whether HG amplifies contralateral myogenic dysfunction and whether loss of tone in the contralateral hemisphere contributes to stroke outcomes remain to be determined. Our hypothesis was that contralateral myogenic dysfunction worsens stroke outcomes after acute hyperglycemic stroke in an oxidative stress-dependent manner. Male wild-type or SOD1 transgenic rats were injected with saline or 40% glucose solution 10 min before surgery and then subjected to 30 min of ischemia/45 min or 24 h of reperfusion. In another set of animals (n = 5), SOD1 was overexpressed only in the contralateral hemisphere by stereotaxic adenovirus injection 2-3 wk before I/R. Myogenic tone and neurovascular outcomes were determined. HG exacerbated myogenic dysfunction in contralateral side only, which was associated with infarct size expansion, increased edema, and more pronounced neurological deficit. Global and selective SOD1 overexpression restored myogenic reactivity in ipsilateral and contralateral sides, respectively, and enhanced neurovascular outcomes. In conclusion, our results show that SOD1 overexpression nullified the detrimental effects of HG on myogenic tone and stroke outcomes and that the contralateral hemisphere may be a novel target for the management of acute hyperglycemic stroke.
authors.affiliation: Department of Physiology, Georgia Regents University, Augusta, Georgia;
authors.forename: Maha
authors.initials: M
authors.lastname: Coucha
authors.affiliation: Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia; Department of Physiology, Georgia Regents University, Augusta, Georgia;
authors.forename: Weiguo
authors.initials: W
authors.lastname: Li
authors.affiliation: Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia; Program in Clinical and Experimental Therapeutics, University of Georgia College of Pharmacy, Augusta, Georgia.
authors.forename: Sherif
authors.initials: S
authors.lastname: Hafez
authors.affiliation: Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia; Department of Physiology, Georgia Regents University, Augusta, Georgia;
authors.forename: Mohammed
authors.initials: M
authors.lastname: Abdelsaid
authors.affiliation: Department of Biostatistics, Georgia Regents University, Augusta, Georgia;
authors.forename: Maribeth H
authors.initials: MH
authors.lastname: Johnson
authors.affiliation: Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia; Department of Neurology, Georgia Regents University, Augusta, Georgia; and Program in Clinical and Experimental Therapeutics, University of Georgia College of Pharmacy, Augusta, Georgia.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Fagan
authors.affiliation: Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia; Department of Physiology, Georgia Regents University, Augusta, Georgia; Program in Clinical and Experimental Therapeutics, University of Georgia College of Pharmacy, Augusta, Georgia aergul@gru.edu.
authors.forename: Adviye
authors.initials: A
authors.lastname: Ergul
mesh_terms: D000818:Animals; D006943:Hyperglycemia / Q000150:complications* / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020521:Stroke / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: admission hyperglycemia; contralateral hemisphere; ischemia-reperfusion injury; myogenic tone; stroke outcomes; superoxide dismutase