Abstract 220: Contralateral Myogenic Dysfunction Contributes to Stroke Outcomes after Acute Hyperglycemic Stroke

Abstract

Background: Admission hyperglycemia (HG) amplifies vascular injury and neurological deficit in acute ischemic stroke but the mechanism remains controversial. We recently reported that copper/zinc-superoxide dismutase (SOD1) overexpression preserves the myogenic tone of ischemic arteries, achieving neurovascular protection after ischemia/reperfusion (I/R) with or without HG. Experimental studies showed that I/R impairs myogenic response in ischemic and contralateral hemispheres. However, the impact of HG on contralateral vascular reactivity and its role in stroke outcomes still unexplored. Hypothesis: Contralateral myogenic dysfunction worsens stroke outcomes after acute hyperglycemic stroke. Methods: SOD1 adenovirus or an empty vector was stereotaxicly injected in the contralateral hemisphere of control Wistar rats. 2-3 weeks after injection, acute hyperglycemic stroke was induced by injecting saline or 40% glucose solution 10 min before 30 min ischemia/45 min or 24 hr reperfusion. Myogenic tone and neurovascular outcomes were determined. Results: HG exacerbated loss of myogenic tone in contralateral side only (p<0.0001), which was associated with infarct size expansion, increased edema (p<0.05) and more pronounced neurological deficit (p<0.01). Contralateral SOD1 overexpression restored myogenic reactivity in contralateral side only. Cerebral blood flow after reperfusion was increased in both sides (p<0.01), which was accompanied with better neurovascular outcomes (p<0.01). Conclusion: Our results showed that SOD1 overexpression nullified the detrimental effects of HG on contralateral myogenic dysfunction and stroke outcomes, and that contralateral hemisphere may be a novel target for the management of acute hyperglycemic stroke.