Docosahexaenoic acid complexed to albumin elicits high-grade ischemic neuroprotection

Ludmila Belayev, Victor L. Marcheselli, Larissa Khoutorova, Elena B. Rodriguez De Turco, Raul Busto, Myron Ginsberg, Nicolas G. Bazan

Research output: Contribution to journalArticle

108 Citations (Scopus)

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, 10,17S-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.

Original languageEnglish
Pages (from-to)118-123
Number of pages6
JournalStroke
Volume36
Issue number1
DOIs
StatePublished - Jan 1 2005

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Docosahexaenoic Acids
Albumins
Neuroprotection
Ischemia
Middle Cerebral Artery Infarction
Brain Edema
Cerebral Infarction
Omega-3 Fatty Acids
Brain Ischemia
Unsaturated Fatty Acids
Infarction
Sutures
Heart Failure
Stroke
Clinical Trials

Keywords

  • Albumins
  • Fatty acids
  • Ischemia
  • Neuroprotection
  • Rats

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Belayev, L., Marcheselli, V. L., Khoutorova, L., Rodriguez De Turco, E. B., Busto, R., Ginsberg, M., & Bazan, N. G. (2005). Docosahexaenoic acid complexed to albumin elicits high-grade ischemic neuroprotection. Stroke, 36(1), 118-123. https://doi.org/10.1161/01.STR.0000149620.74770.2e

Docosahexaenoic acid complexed to albumin elicits high-grade ischemic neuroprotection. / Belayev, Ludmila; Marcheselli, Victor L.; Khoutorova, Larissa; Rodriguez De Turco, Elena B.; Busto, Raul; Ginsberg, Myron; Bazan, Nicolas G.

In: Stroke, Vol. 36, No. 1, 01.01.2005, p. 118-123.

Research output: Contribution to journalArticle

Belayev, L, Marcheselli, VL, Khoutorova, L, Rodriguez De Turco, EB, Busto, R, Ginsberg, M & Bazan, NG 2005, 'Docosahexaenoic acid complexed to albumin elicits high-grade ischemic neuroprotection', Stroke, vol. 36, no. 1, pp. 118-123. https://doi.org/10.1161/01.STR.0000149620.74770.2e
Belayev L, Marcheselli VL, Khoutorova L, Rodriguez De Turco EB, Busto R, Ginsberg M et al. Docosahexaenoic acid complexed to albumin elicits high-grade ischemic neuroprotection. Stroke. 2005 Jan 1;36(1):118-123. https://doi.org/10.1161/01.STR.0000149620.74770.2e
Belayev, Ludmila ; Marcheselli, Victor L. ; Khoutorova, Larissa ; Rodriguez De Turco, Elena B. ; Busto, Raul ; Ginsberg, Myron ; Bazan, Nicolas G. / Docosahexaenoic acid complexed to albumin elicits high-grade ischemic neuroprotection. In: Stroke. 2005 ; Vol. 36, No. 1. pp. 118-123.
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AB - 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.

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