Sensitization to brain antigens after stroke is augmented by lipopolysaccharide
Sensitization to brain antigens after stroke is augmented by lipopolysaccharide
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DOI：
10.1038/sj.jcbfm.9600160
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发表时间：
2005-12-01
影响因子：
6.3
通讯作者：
Ye, ZC
中科院分区：
文献类型：
--
作者：
Becker, KJ;Kindrick, DL;Ye, ZC
中风后，血脑屏障被短暂破坏，允许白细胞进入大脑和脑抗原进入外周循环。因此，全身免疫系统遇到正常隔离的脑抗原可能为中风后发生脑自身免疫反应提供了机会。在这项研究中，我们评估了髓鞘碱性蛋白（MBP）在大脑中动脉闭塞（MCAO）的动物的免疫反应。一些动物在再灌注时接受脂多糖（LPS; lmg/kg）的腹膜内注射以刺激全身炎症反应。在MCAO后1个月，暴露于LPS的动物更可能对MBP致敏（66.7%对22.2%; P=0.007），并且比非LPS治疗的动物具有更深刻和持久的神经功能缺损。暴露于LPS与中风发作后早期共刺激分子B7.1的表达增加（P=0.009）和MCAO后1个月脑萎缩增加（P=0.03）相关。这些数据表明，在中风时受到全身性炎性损伤的动物倾向于对大脑产生自身免疫反应，并且这种反应与更差的结果相关。这些数据可以部分解释为什么中风后感染的患者发病率增加。
After stroke, the blood-brain barrier is transiently disrupted, allowing leukocytes to enter the brain and brain antigens to enter the peripheral circulation. This encounter of normally sequestered brain antigens by the systemic immune system could therefore present an opportunity for an autoimmune response to brain to occur after stroke. In this study, we assessed the immune response to myelin basic protein (MBP) in animals subjected to middle cerebral artery occlusion (MCAO). Some animals received an intraperitoneal injection of lipopolysaccharide (LPS; 1 mg/kg) at reperfusion to stimulate a systemic inflammatory response. At 1 month after MCAO, animals exposed to LPS were more likely to be sensitized to MBP (66.7% versus 22.2%; P=0.007) and had more profound and persistent neurologic deficits than non-LPS-treated animals. Exposure to LPS was associated with increased expression of the costimulatory molecule B7.1 early after stroke onset (P=0.009) and increased brain atrophy 1 month after MCAO (P=0.03). These data suggest that animals subjected to a systemic inflammatory insult at the time of stroke are predisposed to develop an autoimmune response to brain, and that this response is associated with worse outcome. These data may partially explain why patients who become infected after stroke experience increased morbidity.