Acute treatment with docosahexaenoic acid complexed to albumin reduces injury after a permanent focal cerebral ischemia in rats.

Abstract

Docosahexaenoic acid complexed to albumin (DHA-Alb) is highly neuroprotective after temporary middle cerebral artery occlusion (MCAo), but whether a similar effect occurs in permanent MCAo is unknown. Male Sprague-Dawley rats (270-330 g) underwent permanent MCAo. Neurological function was evaluated on days 1, 2 and 3 after MCAo. We studied six groups: DHA (5 mg/kg), Alb (0.63 or 1.25 g/kg), DHA-Alb (5 mg/kg+0.63 g/kg or 5 mg/kg+1.25 g/kg) or saline. Treatment was administered i.v. at 3 h after onset of stroke (n = 7-10 per group). Ex vivo imaging of brains and histopathology were conducted on day 3. Saline- and Alb-treated rats developed severe neurological deficits but were not significantly different from one another. In contrast, rats treated with low and moderate doses of DHA-Alb showed improved neurological score compared to corresponding Alb groups on days 2 and 3. Total, cortical and subcortical lesion volumes computed from T2 weighted images were reduced following a moderate dose of DHA-Alb (1.25 g/kg) by 25%, 22%, 34%, respectively, compared to the Alb group. The total corrected, cortical and subcortical infarct volumes were reduced by low (by 36-40%) and moderate doses (by 34-42%) of DHA-Alb treatment compared to the Alb groups. In conclusion, DHA-Alb therapy is highly neuroprotective in permanent MCAo in rats. This treatment can provide the basis for future therapeutics for patients suffering from ischemic stroke.

• Authors: Tiffany N Eady, Larissa Khoutorova, Daniela V Anzola, Sung-Ha Hong, Andre Obenaus, Alena Mohd-Yusof, Nicolas G Bazan, Ludmila Belayev
• Journal: PloS one (PLoS One) Vol. 8 Issue 10 Pg. e77237 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 24194876 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Albumins
• Neuroprotective Agents
• Docosahexaenoic Acids

Topics

• Administration, Intravenous
• Albumins (administration & dosage, metabolism, pharmacology)
• Analysis of Variance
• Animals
• Docosahexaenoic Acids (administration & dosage, metabolism, pharmacology)
• Dose-Response Relationship, Drug
• Histological Techniques
• Infarction, Middle Cerebral Artery (drug therapy, pathology)
• Male
• Neuroprotective Agents (pharmacology)
• Rats
• Rats, Sprague-Dawley