TY - JOUR
T1 - SOD1 overexpression prevents acute hyperglycemia-induced cerebral myogenic dysfunction
T2 - Relevance to contralateral hemisphere and stroke outcomes
AU - Coucha, Maha
AU - Li, Weiguo
AU - Hafez, Sherif
AU - Abdelsaid, Mohammed
AU - Johnson, Maribeth H.
AU - Fagan, Susan C.
AU - Ergul, Adviye
N1 - Funding Information:
A. Ergul is a Research Career Scientist at the Charlie Norwood Veterans Affairs (VA) Medical Center in Augusta, Georgia. This work was supported in part by VAU.S. Department of Veterans Affairs Merit AwardBX000347, a VA Research Career Scientists Award, and National Institutes of Health (NIH) Grant R01-NS-083559 (to A. Ergul); VAU.S. Department of Veterans Merit AwardBX000891 and National Institutes of Health NIH Grant NS-063965 (to S. C. Fagan); and American Heart Association Predoctoral Fellowship 12PRE11300001 (to M. Coucha).
Funding Information:
part by VA Merit Award BX000347, a VA Research Career Scientists Award, and National Institutes of Health (NIH) Grant R01-NS-083559 (to A. Ergul); VA Merit Award BX000891 and NIH Grant NS-063965 (to S. C. Fagan); and American Heart Association Predoctoral Fellowship 12PRE11300001 (to M. Coucha).
Publisher Copyright:
© 2015 the American Physiological Society.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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.
AB - 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.
KW - Admission hyperglycemia
KW - Contralateral hemisphere
KW - Ischemia-reperfusion injury
KW - Myogenic tone
KW - Stroke outcomes
KW - Superoxide dismutase
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U2 - 10.1152/ajpheart.00321.2014
DO - 10.1152/ajpheart.00321.2014
M3 - Article
C2 - 25552308
AN - SCOPUS:84944407894
SN - 0363-6135
VL - 308
SP - H456-H466
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 5
ER -