Docosahexaenoic acid complexed to albumin elicits high-grade ischemic neuroprotection.
OBJECTIVE
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.
Belayev
Ludmila
L
Cerebral Vascular Disease Research Center, Department of Neurology, University of Miami School of Medicine, Miami, FL 33101, USA.
Marcheselli
Victor L
VL
Khoutorova
Larissa
L
Rodriguez de Turco
Elena B
EB
Busto
Raul
R
Ginsberg
Myron D
MD
Bazan
Nicolas G
NG
D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex; D012709:Serum Albumin / Q000493:pharmacokinetics / Q000627:therapeutic use*
D018696:Neuroprotective Agents; D012709:Serum Albumin; D004281:Docosahexaenoic Acids