The effect of high-dose albumin therapy on local cerebral perfusion after transient focal cerebral ischemia in rats
The effect of high-dose albumin therapy on local cerebral perfusion after transient focal cerebral ischemia in rats
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DOI：
10.1016/s0006-8993(98)00674-x
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发表时间：
1998-08-31
期刊：
影响因子：
2.9
通讯作者：
Ginsberg, MD
中科院分区：
文献类型：
--
作者：
Huh, PW;Belayev, L;Ginsberg, MD
我们已经证明，高浓度白蛋白治疗对局灶性脑缺血具有显著的神经保护作用。本研究旨在确定血流动力学改变对这种治疗效果的影响程度。常温下，生理调节的雄性Sprague-Dawley大鼠接受了2小时的大脑中动脉闭塞（MCAo）插入的管腔内缝线涂聚-L-赖氨酸。在2小时MCAo后，在缝线拔出后立即静脉给予白蛋白（25%人血清白蛋白溶液）或溶剂（0.9%氯化钠），剂量为体重的1%。局部脑血流量（LCBF）测定放射自显影与C-14 -碘安替比林后1小时的再循环。新的图像处理方法被用来比较平均LCBF数据集对以前获得的梗死频率数据的像素逐像素的基础上。白蛋白治疗使平均红细胞压积降低42%，但未产生其他全身性改变。基于像素的组织病理学分析显示，盐水处理的MCAo大鼠中存在大的、一致的皮质和皮质下梗死;白蛋白治疗使平均皮质梗死体积减少了85%。在显示白蛋白相关神经保护的区域内，具有缺血核心血流范围上限的LCBF的像素数（0.12-0.24 ml g（-1）min（-1）），与生理盐水处理的大鼠相比，白蛋白治疗降低了8.6倍;在白蛋白治疗的大鼠中，下半暗带血流范围（0.24-0.36 ml g（-1）min（-1））的LCBF像素数减少了3.1倍（重复测量方差分析p = 0.04）。对[白蛋白-生理盐水]三维差分图像数据集的分析显示，在缺血半球的后部，围绕先前缺血的核心区域，有一个具有统计学显著性的白蛋白相关LCBF增加的环周区。因此，高浓度白蛋白治疗可改善关键LCBF降低区域的局部灌注。然而，这种LCBF效应的空间范围似乎太小，无法完全解释这种疗法的显著神经保护功效。我们认为，其他非血流动力学机制也可能有贡献。(C)1998 Elsevier Science B.V，保留所有权利。
We have shown that high-concentration albumin therapy is markedly neuroprotective in focal cerebral ischemia. The present study was conducted to ascertain the degree to which hemodynamic alterations are responsible for this therapeutic effect. Normothermic, physiologically regulated male Sprague-Dawley rats received a 2-h period of middle cerebral artery occlusion (MCAo) by insertion of an intraluminal suture coated with poly-L-lysine. Albumin (25% human serum albumin solution) or vehicle (0.9% sodium chloride) was administered intravenously at a dose of 1% of body weight immediately after suture withdrawal following 2-h MCAo. Local cerebral blood flow (LCBF) was measured autoradiographically with C-14 - iodoantipyrine after 1 h of recirculation. Novel image-processing methods were used to compare average LCBF data sets against previously obtained infarction-frequency data on a pixel-by-pixel basis. Albumin therapy reduced mean hematocrit by 42% but produced no other systemic alterations. Pixel-based histopathological analysis revealed large, consistent cortical and subcortical infarcts in saline-treated rats with MCAo; albumin therapy reduced mean cortical infarct volume by 85%. Within regions showing albumin-associated neuroprotection, numbers of pixels having LCBF in the upper ischemic-core flow range (0.12-0.24 ml g(-1) min(-1)) were reduced by 8.6-fold by albumin therapy when compared to saline-treated rats; and numbers of pixels with LCBF in the lower penumbral flow range (0.24-0.36 ml g(-1) min(-1)) were reduced by 3.1-fold in albumin-treated rats (p = 0.04 by repeated-measures analysis of variance). Analysis of the [albumin-saline] 3-dimensional difference-image data set revealed a circumferential zone of statistically significant albumin-associated LCBF increase within the posterior portion of the ischemic hemisphere, surrounding the core-region of prior ischemia. Thus, high-concentration albumin therapy improves local perfusion to regions of critical LCBF reduction. The spatial extent of this LCBF effect, however, appears too small to account fully for the marked neuroprotective efficacy of this therapy. We suggest that other, non-hemodynamic mechanisms may also be contributory. (C) 1998 Elsevier Science B.V, All rights reserved.