Docosahexaenoic Acid Complexed to Albumin Elicits High-Grade Ischemic Neuroprotection
- 1 January 2005
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Stroke
- Vol. 36 (1), 118-123
- https://doi.org/10.1161/01.str.0000149620.74770.2e
Abstract
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, 10,17 S -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.Keywords
This publication has 36 references indexed in Scilit:
- Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemiaAnnals of Neurology, 2003
- Neuroprotective Effect of SolCD39, a Novel Platelet Aggregation Inhibitor, on Transient Middle Cerebral Artery Occlusion in RatsStroke, 2003
- New perspectives on developing acute stroke therapyAnnals of Neurology, 2002
- Toward Wisdom From FailureStroke, 2002
- Posttreatment With High-Dose Albumin Reduces Histopathological Damage and Improves Neurological Deficit Following Fluid Percussion Brain Injury in RatsJournal of Neurotrauma, 1999
- Tissue Plasminogen Activator for Acute Ischemic StrokeNew England Journal of Medicine, 1995
- Docosahexaenoic acid (22:6, n-3) is metabolized to lipoxygenase reaction products in the retinaBiochemical and Biophysical Research Communications, 1984
- Polyunsaturated fatty acids of the retinaProgress in Lipid Research, 1981
- Displacement into incubation medium by albumin of highly unsaturated retina free fatty acids arising from membrane lipidsFEBS Letters, 1974
- Effects of ischemia and electroconvulsive shock on free fatty acid pool in the brainBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1970