Published Online
on November 29, 2004

A more recent version of this article appeared on January 1, 2005

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Submitted on August 19, 2004
Revised on September 29, 2004
Accepted on October 5, 2004

Docosahexaenoic Acid Complexed to Albumin Elicits High-Grade Ischemic Neuroprotection

Ludmila Belayev MD; Victor L. Marcheselli PhD; Larissa Khoutorova BS; Elena B. Rodriguez de Turco PhD; Raul Busto BS; Myron D. Ginsberg MD^*; and Nicolas G. Bazan MD, PhD

From the Cerebral Vascular Disease Research Center (L.B., L.K., R.B., M.D.G.), Department of Neurology, University of Miami School of Medicine, Miami, FL; and the Neuroscience Center of Excellence and Department of Ophthalmology (V.L.M., E.B.R.d.T., N.G.B.), Louisiana State University Health Sciences Center, New Orleans, La.

^* To whom correspondence should be addressed. E-mail: mdginsberg{at}stroke.med.miami.edu.

Background and Purpose--High-dose human albumin therapy is strongly neuroprotective in models of brain ischemia and trauma and is currently being studied in a pilot-phase clinical stroke trial. Among its actions in ischemia, albumin induces the systemic mobilization of n-3 polyunsaturated fatty acids and may help to replenish polyunsaturated fatty acids lost from neural membranes.

Methods--We complexed 25% human albumin to docosahexaenoic acid (DHA; 22:6n-3) and compared its neuroprotective efficacy with that of native albumin in rats with 2-hour focal ischemia produced by intraluminal suture-occlusion of the middle cerebral artery.

Results--In animals treated with DHA-albumin, 0.63 g/kg, the improvement in neurobehavioral scores at 72 hours significantly exceeded that of other treatment groups, and the extent of histological protection (86% reduction in cortical infarction) was highly significant and tended to surpass the degree of cortical protection produced by native albumin at 1.25 g/kg (65%). DHA-albumin 0.63 g/kg, but not native albumin, also significantly reduced subcortical infarction and markedly diminished brain swelling. Lipidomic analysis of DHA-albumin-treated postischemic brains revealed a large accumulation of the neuroprotective DHA metabolite, 10,17S-docosatriene, in the ipsilateral hemisphere.

Conclusions--The high-grade neuroprotection afforded by the DHA-albumin complex at relatively low albumin doses is clinically advantageous in that it might reduce the likelihood of acute intravascular volume overload and congestive heart failure sometimes induced when patients with compromised cardiovascular function are treated with high-dose albumin.

Key words: albumins • ischemia • fatty acids • neuroprotection • rats

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