Transient blockage of the CD11d/CD18 integrin reduces contusion volume and macrophage infiltration after traumatic brain injury in rats
Transient blockage of the CD11d/CD18 integrin reduces contusion volume and macrophage infiltration after traumatic brain injury in rats
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DOI：
10.1016/j.brainres.2008.02.057
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发表时间：
2008-05-01
期刊：
影响因子：
2.9
通讯作者：
Dietrich, W. Dalton
中科院分区：
文献类型：
--
作者：
Utagawa, Akira;Bramlett, Helen M.;Dietrich, W. Dalton
创伤性脑损伤（TBI）早期的炎症反应可导致继发性损害。本研究的目的是评价采用CD 11 d/CD 18整合素阻断性单克隆抗体（mAb）进行短暂治疗对TBI后组织病理学结果和巨噬细胞浸润的影响。在雄性Sprague-Dawley大鼠中诱导了旁脑室液压冲击（FP）脑损伤（1.8-2.1 atm）。将大鼠随机分为两个创伤组，治疗组（N = 7）和未治疗组（N = 8）动物。在治疗组中，在脑损伤后30 min、24和48 h给予针对CD 11 d/CD 18整合素的CD 11 d亚基的mAb。对照动物使用相同的剂量和治疗方案接受同种型匹配的不相关mAb。在TBI后3天，将动物灌注固定用于组织病理学和免疫细胞化学分析。与溶剂处理的动物相比，抗CD 11 d mAb处理减少了挫伤面积以及总挫伤体积。例如，总挫伤体积从2.7 +/- 0.5 mm（3）（平均值+/- SEM）减少到1.4 +/- 0.4（p < 0.05）。识别CD 68免疫反应性巨噬细胞的免疫细胞化学研究表明，治疗导致白细胞浸润到挫伤皮质区的显着衰减。这些数据强调了阻断炎性细胞募集到损伤的脑中对创伤性脑损伤后的组织病理学结果的有益作用。(C)2008 Elsevier B. V.保留所有权利。
The early inflammatory response to traumatic brain injury (TBI) may result in secondary damage. The purpose of this study was to evaluate the effects of a transient treatment employing a blocking monoclonal antibody (mAb) to the CD11d/CD18 integrin on histopathological outcome and macrophage infiltration following TBI. A parasagittal fluid percussion (FP) brain injury (1.8-2.1 atm) was induced in male Sprague-Dawley rats. Rats were randomized into two trauma groups, treated (N = 7) and nontreated (N = 8) animals. In the treated group, a mAb to the CD11d subunit of the CD11d/CD18 integrin was administered 30 min, 24 and 48 h after brain injury. Control animals received an isotype-matched irrelevant mAb using the same dose and treatment regimen. At 3 days after TBI, animals were perfusion-fixed for histopathological and immunocytochemical analysis. The anti-CD11d mAb treatment reduced contusion areas as well as overall contusion volume compared to vehicle treated animals. For example, overall contusion volume was reduced from 2.7 +/- 0.5 mm(3) (mean +/- SEM) to 1.4 +/- 0.4 with treatment (p < 0.05). Immunocytochemical studies identifying CD68 immunoreactive macrophages showed that treatment caused significant attenuation of leukocyte infiltration into the contused cortical areas. These data emphasize the beneficial effects of blocking inflammatory cell recruitment into the injured brain on histopathological outcome following traumatic brain injury. (C) 2008 Elsevier B.V. All rights reserved.