Abstract W MP89: Silencing VEGF-B Diminishes the Neuroprotective Effect of Candesartan Treatment after Experimental Focal Cerebral Ischemia
Background & Objective: The pro-survival effect of VEGF-B has been documented in different in vivo and in vitro models. We have previously shown an enhanced VEGF-B expression in response to candesartan treatment after focal cerebral ischemia. In this study, we tested the hypothesis that VEGF-B expression contributes to candesartan-mediated recovery.
Methods: Silencing VEGF-B expression was achieved by bilateral intracerebroventricular injection of lentiviral particles containing short hairpin RNA against VEGF-B (KD) or vehicle (NTC). Middle cerebral artery (MCA) was occluded for 90 minutes. At reperfusion, animals received either intravenous saline or candesartan. Neurobehavioral outcome was assessed 24, 48 and 72 hours after the insult and infarct size was measured at 72 hours. In an additional set of experiment, middle cerebral artery was occluded for 3h followed by 21h reperfusion. Rats were sacrificed at 24h post-MCAO and brains perfused for evaluation of vascular markers (edema and hemoglobin content).
Results (Table): Candesartan-treated animals showed a significant reduction in the infarct size and edema accompanied by functional recovery in Bederson, beam walk, paw grasp and grip strength performance only in the presence of VEGF-B. In addition, candesartan-treated animals showed significantly reduction of hemoglobin content, a marker for hemorrhage and edema at 24 h after MCAO.
Conclusion: Our results suggest VEGF-B plays a critical role in mediating candesartan’s neuronal and vascular protective effect after stroke. Identifying growth factors that mediate recovery after ischemic stroke presents possible targets for stroke therapeutics.
Author Disclosures: S. Soliman: None. T. Ishrat: None. B. Pillai: None. A. Ergul: None. S.C. Fagan: 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.
- © 2015 by American Heart Association, Inc.