Docosahexaenoic acid complexed to albumin provides neuroprotection after experimental stroke in aged rats

Abstract

Recently we have shown that docosahexaenoic acid complexed to albumin (DHA-Alb) is neuroprotective after experimental stroke in young rats. The purpose of this study was to determine whether treatment with DHA-Alb would be protective in aged rats after focal cerebral ischemia. Isoflurane/nitrous oxide-anesthetized normothermic (brain temperature 36-36.5. °C) Sprague-Dawley aged rats (18-months old) received 2. h middle cerebral artery occlusion (MCAo) by poly- l-lysine-coated intraluminal suture. The neurological status was evaluated during occlusion (60. min) and on days 1, 2, 3 and 7 after MCAo; a grading scale of 0-12 was employed. DHA (5. mg/kg), Alb (0.63. g/kg), DHA-Alb (5. mg/kg + 0.63. g/kg) or saline was administered i.v. 3. h after onset of stroke (n = 8-10 per group). Ex vivo T2-weighted imaging (T2WI) of the brains was conducted on an 11.7T MRI on day 7 and 3D reconstructions were generated. Infarct volumes and number of GFAP (reactive astrocytes), ED-1 (activated microglia/microphages), NeuN (neurons)-positive cells and SMI-71 (positive vessels) were counted in the cortex and striatum at the level of the central lesion. Physiological variables were entirely comparable between groups. Animals treated with DHA-Alb showed significantly improved neurological scores compared to vehicle rats; 33% improvement on day 1; 39% on day 2; 41% on day 3; and 45% on day 7. Total and cortical lesion volumes computed from T2WI were significantly reduced by DHA-Alb treatment (62 and 69%, respectively). In addition, treatment with DHA-Alb reduced cortical and total brain infarction while promoting cell survival. We conclude that DHA-Alb therapy is highly neuroprotective in aged rats following focal cerebral ischemia and has potential for the effective treatment of ischemic stroke in aged individuals. © 2013 Elsevier Inc.