Docosahexaenoic acid complexed to human albumin in experimental stroke: neuroprotective efficacy with a wide therapeutic windowReport as inadecuate




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Experimental and Translational Stroke Medicine

, 4:19

First Online: 14 September 2012Received: 02 August 2012Accepted: 06 September 2012

Abstract

BackgroundDocosahexaenoic acid DHA complexed to human serum albumin Alb is neuroprotective after experimental stroke. Here we tested using lower concentrations of albumin as part of the complex to achieve neuroprotection. We found that lower Alb concentrations extend the therapeutic window of protection beyond 5 h after stroke onset.

MethodsSprague–Dawley rats were received 2 h middle cerebral artery occlusion MCAo. The behavior was evaluated on day 1, 2, 3 and 7 after MCAo. In the dose–response study, animals were given either DHA 5mg-kg, Alb 0.63g-kg, DHA-Alb 5mg-kg + 0.32, 0.63 or 1.25 g-kg or saline, i.v. 3 h after onset of stroke n=6-8 per group. In the therapeutic window study, DHA-Alb 5mg-kg + 1.25g-kg was administered i.v. at either 3, 4, 5, 6 or 7 h after onset of stroke n=7-9 per group. Alb 1.25g-kg was given at 3 h or 5 h and saline at 3h after onset of reperfusion. Seven days after MCAo, infarct volumes and number of GFAP, ED-1, NeuN, SMI-71 positive cells and vessels were counted.

ResultsModerate DHA-Alb doses 0.63 and 1.25 g-kg improved neurological scores compared to albumin-treated rats on days 1, 2, 3 and 7. All DHA-Alb doses 0.32, 0.63 and 1.25 g-kg markedly reduced cortical by 65-70%, striatal by 52-63% and total infarct volumes by 60-64% compared to native Alb group. In the therapeutic window study DHA-Alb led to improved neurological score and significant reductions of infarct volumes especially in the cortical or penumbral region, even when treatment was initiated as late as 7 hours after onset of MCAo.

ConclusionsThe DHA-Alb complex affords high-grade neurobehavioral neuroprotection in focal cerebral ischemia, equaling or exceeding that afforded by native Alb or DHA, at considerably moderate doses. It has a broad therapeutic window extending to 7 h after stroke onset. Taken together, these finding support the potential clinical feasibility of administering DHA-Alb therapy to patients with acute ischemic stroke.

KeywordsPenumbra DHA-Alb complex Neuroprotection Behavior Histopathology Focal ischemia Experimental stroke Electronic supplementary materialThe online version of this article doi:10.1186-2040-7378-4-19 contains supplementary material, which is available to authorized users.

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Author: Tiffany N Eady - Larissa Khoutorova - Kristal D Atkins - Nicolas G Bazan - Ludmila Belayev

Source: https://link.springer.com/



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