Abstract W P358: SOD overexpression Accounts for the Neurovascular Protection in Rats Following Ischemic Stroke
Acute hyperglycemic stroke (AHS) is associated with poor stroke outcomes and functional recovery. We recently showed that myogenic response; the ability of blood vessels to maintain adequate blood flow despite changes in pressure; was impaired after AHS. Experimental studies showed that acute elevation of blood glucose at stroke onset enhances oxidative stress that impairs effective reperfusion. Copper/zinc-superoxide dismutase (SOD1), an antioxidant enzyme that catalyzes the dismutation of superoxide into oxygen and hydrogen peroxide, has been shown to be highly protective against ischemia/reperfusion injury (IRI). Yet, the mechanism by which SOD1 improves stroke outcomes is still unresolved.
Hypothesis: SOD1 overexpression improves cerebral myogenic behavior leading to neurovascular protection after AHS
Methods: Wild-type Sprague Dawley (SD) and human SOD1 transgenic rats (n=6-8) were subjected to 30 min middle cerebral artery occlusion (MCAO)/45 min or 24 hr reperfusion. Hyperglycemia was induced by intraperitoneal injection of 40 % glucose solution 10 min before procedure. Myogenic tone of isolated MCAs, infarct size, edema and neurological deficits were determined.
Results: IRI impaired myogenic response of MCAs isolated from SD rats compared to sham (***p<0.001). Normoglycemic and hyperglycemic SOD1 rats maintained a well developed myogenic response after IRI. Infarct size and edema were significantly reduced in the SOD1 transgenic rats compared to SD rats (**p<0.01). SOD1 overexpression significantly improved beam walk score and grip strength deficit compared to SD rats (*p<0.05). Hyperglycemic SOD1 transgenic rats showed smaller infarct size and edema (**p<0.01) and experienced improved neurological behavior (*p<0.05) compared to hyperglycemic SD rats.
Conclusions: We provide evidence that SOD1 overexpression preserves the myogenic behavior of MCAs achieving neurovascular protection in conditions associated with poor stroke outcomes. Further studies are required to unravel the exact mechanism by which SOD exerts its beneficial role on vascular reactivity, and to identify new therapeutic targets for stroke management.
Author Disclosures: M. Coucha: None. W. Li: None. M. Abdelsaid: None. S. Hafez: None. S.C. Fagan: None. A. Ergul: None.
This research has received full or partial funding support from the American Heart Association, Greater Southeast Affiliate – Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico, Tennessee, U.S. Virgin Islands.
- © 2014 by American Heart Association, Inc.