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Abstract
Background: Recently we have shown that docosahexaenoic acid (DHA), a component of fish oil, complexed to human serum albumin (Alb) is highly neuroprotective after experimental stroke in young rats. The purpose of this study was to determine whether treatment with DHA-Alb complex would be protective in aged rats after focal cerebral ischemia. Methods and Results: Isoflurane/nitrous oxide-anesthetized normothermic (brain temperature 36-36.5 o 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 (normal score=0, maximal deficit=12). DHA (5mg/kg), Alb (0.63g/kg), DHA-Alb (5mg/kg+0.63g/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. Conclusions: 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.
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