Belayev Ludmila, Marcheselli Victor L, Khoutorova Larissa, Rodriguez de Turco Elena B, Busto Raul, Ginsberg Myron D, Bazan Nicolas G
Cerebral Vascular Disease Research Center, Department of Neurology, University of Miami School of Medicine, Miami, FL 33101, USA.
Stroke. 2005 Jan;36(1):118-23. doi: 10.1161/01.STR.0000149620.74770.2e. Epub 2004 Nov 29.
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.
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.
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.
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.
高剂量人白蛋白疗法在脑缺血和创伤模型中具有强大的神经保护作用，目前正在一项临床中风试验的试点阶段进行研究。在缺血过程中，白蛋白可诱导n-3多不饱和脂肪酸的全身动员，并可能有助于补充神经膜中丢失的多不饱和脂肪酸。
我们将25%的人白蛋白与二十二碳六烯酸（DHA；22:6n-3）复合，并将其神经保护效果与天然白蛋白在通过大脑中动脉腔内缝合闭塞产生2小时局灶性缺血的大鼠中的效果进行比较。
在用0.63 g/kg DHA-白蛋白治疗的动物中，72小时时神经行为评分的改善显著超过其他治疗组，组织学保护程度（皮质梗死减少86%）非常显著，且往往超过1.25 g/kg天然白蛋白产生的皮质保护程度（65%）。0.63 g/kg的DHA-白蛋白，但不是天然白蛋白，也显著减少了皮质下梗死，并明显减轻了脑肿胀。对DHA-白蛋白治疗的缺血后大脑进行脂质组学分析发现，在同侧半球中神经保护DHA代谢物10,17S-二十二碳三烯大量积累。
DHA-白蛋白复合物在相对较低的白蛋白剂量下提供的高级神经保护在临床上具有优势，因为它可能降低心血管功能受损的患者在接受高剂量白蛋白治疗时有时会出现的急性血管内容量超负荷和充血性心力衰竭的可能性。
