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Experimental & Translational Stroke Medicine
Published in: Experimental & Translational Stroke Medicine 1/2015

Open Access 01-12-2015 | Research

Docosahexaenoic acid improves behavior and attenuates blood–brain barrier injury induced by focal cerebral ischemia in rats

Authors: Sung-Ha Hong, Larissa Khoutorova, Nicolas G Bazan, Ludmila Belayev

Published in: Experimental & Translational Stroke Medicine | Issue 1/2015

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Abstract

Background

Ischemic brain injury disrupts the blood–brain barrier (BBB) and then triggers a cascade of events, leading to edema formation, secondary brain injury and poor neurological outcomes. Recently, we have shown that docosahexaenoic acid (DHA) improves functional and histological outcomes following experimental stroke. However, little is known about the effect of DHA on BBB dysfunction after cerebral ischemia-reperfusion injury. The present study was designed to determine whether DHA protects against BBB disruption after focal cerebral ischemia in rats.

Methods

Physiologically-controlled SD rats received 2 h middle cerebral artery occlusion (MCAo). DHA (5 mg/kg) or vehicle (saline) was administered I.V. at 3 h after onset of MCAo. Fluorometric quantitation of Evans Blue dye (EB) was performed in eight brain regions at 6 h, 24 h or 72 h after MCAo. Fluorescein isothiocynate (FITC) - dextran leakage and histopathology was evaluated on day 3 after stroke.

Results

Physiological variables were stable and showed no significant differences between groups. DHA improved neurological deficits at 24 h, 48 h and 72 h and decreased EB extravasation in the ischemic hemisphere at 6 h (by 30%), 24 h (by 48%) and 72 h (by 38%). In addition, 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. DHA treatment attenuated cortical (by 50%) and total infarct volume (by 38%) compared to vehicle-treated rats on day 3 after stroke.

Conclusions

DHA therapy diminishes BBB damage accompanied with the acceleration of behavioral recovery and attenuation of the infarct volume. It is reasonable to propose that DHA has the potential for treating focal ischemic stroke in the clinical setting.
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Metadata
Title
Docosahexaenoic acid improves behavior and attenuates blood–brain barrier injury induced by focal cerebral ischemia in rats
Authors
Sung-Ha Hong
Larissa Khoutorova
Nicolas G Bazan
Ludmila Belayev
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Experimental & Translational Stroke Medicine / Issue 1/2015
Electronic ISSN: 2040-7378
DOI
https://doi.org/10.1186/s13231-014-0012-0