Albumin treatment reduces neurological deficit and protects blood-brain barrier integrity after acute intracortical hematoma in the rat
Albumin treatment reduces neurological deficit and protects blood-brain barrier integrity after acute intracortical hematoma in the rat
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DOI：
10.1161/01.str.0000152949.31366.3d
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发表时间：
2005-02-01
期刊：
影响因子：
8.3
通讯作者：
Ginsberg, MD
中科院分区：
文献类型：
--
作者：
Belayev, L;Saul, I;Ginsberg, MD
背景和目的--急性脑出血(ICH)是一种常见且严重的卒中类型。到目前为止，对脑出血的医疗管理对发病率和死亡率几乎没有影响。由于白蛋白治疗在缺血性卒中的临床前模型中具有明显的神经保护作用，并且由于缺血性卒中和出血性卒中具有共同的损伤机制，我们假设白蛋白治疗也可能有益于脑出血。方法：在麻醉的常温大鼠中，通过一次立体定向注射50微升的自体非肝素化全血5分钟，造成急性皮质内血肿。各组动物分别于脑出血后60分钟注射25%人血清白蛋白1.25g/kg或静脉注射生理盐水。在接下来的2到7天内，对神经行为进行顺序量化。结果：脑出血后50min，所有大鼠均出现高度神经功能障碍(评分10.3+/-0.2，平均+/-扫描电子显微镜评分12分)。与生理盐水处理的大鼠相比，白蛋白处理的大鼠表现出改善的神经评分，从治疗后的几个小时开始，并持续到7天的存活期。在第3天和第7天，白蛋白组的平均总神经评分比生理盐水处理组低38%到43%。在盐水处理的脑出血大鼠，血肿周围的伊文思蓝变色很明显，但经白蛋白治疗后，血肿周围的伊文思蓝变色减轻。经白蛋白治疗后，血肿同侧大脑半球伊文思蓝含量降低49%(白蛋白93.9+/-13.3vs生理盐水184.7+/-33.7 mg/g，P<；0.05)。白蛋白治疗不影响血肿体积和脑肿胀。结论：及时白蛋白治疗可改善急性皮质内血肿患者的神经功能和血脑屏障的完整性。这些观察结果具有重要的潜在临床意义。
Background and Purpose - Acute intracerebral hemorrhage (ICH) is a common and severe form of stroke. To date, medical management of ICH has had scant impact on morbidity and mortality. Because albumin therapy is markedly neuroprotective in preclinical models of ischemic stroke, and because ischemic and hemorrhagic stroke share several common injury mechanisms, we hypothesized that albumin therapy might also benefit ICH.Methods - Acute intracortical hematoma was produced in anesthetized, normothermic rats by the single stereotaxic injection of 50 muL of autologous, nonheparinized whole blood over 5 minutes. Separate animal groups were treated either with 25% human albumin, 1.25 g/kg, or with intravenous saline vehicle at 60 minutes after ICH. Neurobehavior was quantified sequentially over the next 2 to 7 days. Damage to the blood - brain barrier was assessed at 2 days after ICH by fluorometric measurement of Evans blue extravasation in dissected brain regions.Results - High-grade neurological deficits were present in all rats at 50 minutes after ICH ( score 10.3 +/- 0.2, mean +/- SEM [ maximal score 12]). Albumin-treated rats showed improved neuroscores relative to saline-treated animals beginning within hours of treatment and persisting throughout the 7-day survival period. At 3 and 7 days, mean total neuroscores of the albumin group were 38% to 43% lower than in saline-treated animals. Perihematomal Evans blue discoloration was readily evident in saline-treated ICH rats but was reduced by albumin treatment. Hemispheric Evans blue content ipsilateral to the hematoma was reduced by 49% by albumin treatment ( albumin 93.9 +/- 13.3 versus saline 184.7 +/- 33.7 mg/g, P < 0.05). Hematoma volume and brain swelling were not affected by albumin treatment.Conclusions - Prompt albumin therapy improves neurological function and blood - brain barrier integrity after acute intracortical hematoma. These observations have important potential clinical implications.