Robust Docosahexaenoic Acid–Mediated Neuroprotection in a Rat Model of Transient, Focal Cerebral Ischemia

Abstract

Background and Purpose-Docosahexaenoic acid (DHA; 22:6n-3), an -3 essential fatty acid family member, is the precursor of neuroprotectin D1, which downregulates apoptosis and, in turn, promotes cell survival. This study was conducted to assess whether DHA would show neuroprotective efficacy when systemically administered in different doses after middle cerebral artery occlusion (MCAo) in rats. Methods-Sprague-Dawley rats were anesthetized with isoflurane and subjected to 2 hour of MCAo. Animals were treated with either DHA (low dosesϭ3.5 or 7 mg/kg; medium dosesϭ16 or 35 mg/kg; and high doseϭ70 mg/kg) or an equivalent volume of saline intravenously 3 hours after MCAo onset. Neurologic status was evaluated during occlusion (60 minutes) and on days 1, 2, 3, and 7 after MCAo. Seven days after MCAo, brains were perfusion-fixed, and infarct areas and volumes were determined. Results-Only the low and medium doses of DHA significantly improved the neurologic score compared with vehicle-treated rats at 24 hours, 48 hours, 72 hours, and 7 days. DHA markedly reduced total corrected infarct volume in all treated groups compared with vehicle-treated rats (3.5 mg/kg, 26Ϯ9 mm 3 ; 7 mg/kg, 46Ϯ12 mm 3 ; 16 mg/kg, 37Ϯ5 mm 3 ; and 35 mg/kg, 34Ϯ15 mm 3 vs vehicle, 94Ϯ12 mm 3 ). Cortical and striatal infarct volumes were also significantly reduced by treatment with DHA. No neuroprotective effects were observed with 70 mg/kg DHA. Conclusions-We conclude that DHA experimental therapy at low and medium doses improves neurologic and histologic outcomes after focal cerebral ischemia and might provide benefits in patients after ischemic stroke.

Omega-3 Polyunsaturated Fatty Acid Supplementation Improves Neurologic Recovery and Attenuates White Matter Injury after Experimental Traumatic Brain Injury

“…Among the many dietary supplements explored to date, omega-3 polyunsaturated fatty acids (o-3 PUFAs) have shown great promise in conferring protection against several neurologic disorders. [1][2][3][4][5] Moreover, dietary supplementation with o-3 PUFA, such as fish oil, in humans is extremely safe and can be ingested over long term as a prophylactic measure. 6 In other words, healthy individuals can ingest fish oil capsules on a daily basis as a preventive measure towards brain injuries.…”

“…[1][2][3] In view of its manifold effects, dietary supplementation with o-3 PUFAs is likely to also ameliorate deleterious effects of TBI on brain function. To date, there are limited investigations on the impact of dietary supplementation with o-3 PUFAs on TBI.…”

A novel therapeutic strategy for experimental stroke using docosahexaenoic acid complexed to human albumin

“…We have shown that NPD1 inhibits brain ischemia-reperfusion-mediated leukocyte infiltration and proinflammatory gene expression, and promotes cell survival both in vitro and in vivo (Bazan, 2007;Belayev et al, 2011;Marcheselli et al, 2003). Our recent studies demonstrated that DHA therapy in medium (5 mg/kg) dose improved neurological and histological outcome when treatment is initiated as late as 5 h after onset of stroke (Belayev et al, 2009(Belayev et al, , 2001). …”

AceDoPC, a structured phospholipid to target the brain with docosahexaenoic acid

“…It has been previously shown that non-esterified DHA, injected to rats after induction of an ischemic stroke, is able to improve the post-stroke status of the animals (Belayev et al, 2009). Using a similar approach in the rat we compared the effect of AceDoPC r and non-esterified DHA injected 1h following the induction of stroke.…”