Abstract T P222: Docosahexaenoic Acid as a Promising Neuroprotectant in Brain Ischemia: New Experimental Evidence

Abstract

Introduction: Docosahexaenoic acid (DHA; 22:6n-3) is an omega-3 essential fatty acid family member and the precursor of neuroprotectin D1, a lipid mediator which downregulates apoptosis and promotes cell survival. Recently, we have shown that DHA improved behavior in animals allowed to survive for 7 d after stroke. This study was conducted to establish whether the behavioral improvement induced by DHA persists with chronic survival. In addition, we examined the effect of DHA on blood-brain barrier (BBB) integrity using Evans Blue (EB) and FITC-dextran markers. METHODS: Physiologically-controlled SD rats received 2 h middle cerebral artery occlusion (MCAo). DHA (5 mg/kg; n=10) or vehicle (saline; n=9) was administered i.v. at 3 h after onset of MCAo. In behavioral studies, the composite 12-point neuroscore, rota-rod, Y-maze and beam walking test were conducted 1, 2 and 3 weeks after MCAo. Ex vivo imaging of the brains and histopathology were carried out on day 21. In BBB studies, fluorometric quantitation of Evans Blue (EB) was performed in six brain regions at 6, 24 or 72 h after stroke. FITC dextran leakage was analyzed on day 3 after MCAo. RESULTS: Physiological variables were stable and showed no significant differences between groups. DHA treatment significantly improved the 12-point neuroscore compared to vehicle on day 1 (by 16%), day 2 (by 19%), day 3 (by 22%), week 1 (by 20%), week 2 (by 22%) and week 3 (by 33%) respectively. Treatment with DHA prolonged latency time in the rota-rod test on weeks 1-3 (by 44-68%), enhanced the score in the balance beam (by 29%) and improved Y-maze performance by 19% compared to the saline group. DHA decreased EB extravasation in the posterior ischemic hemisphere at 6 h (by 34%), 24 h (by 42%) and 72 h (by 38%). EB extravasation was decreased by DHA in the cortex and total hemisphere as well. FITC dextran leakage was reduced by DHA treatment on day 3 by 68% compared to the saline group. CONCLUSION: DHA therapy accelerates long-lasting behavioral recovery and diminishes BBB damage in a model of experimental stroke. Thus, it is reasonable to hypothesize that DHA may have potential use in treating focal ischemic stroke in the clinical setting.