Alterations in blood-brain barrier ICAM-1 expression and brain microglial activation after λ-carrageenan-induced inflammatory pain
Alterations in blood-brain barrier ICAM-1 expression and brain microglial activation after λ-carrageenan-induced inflammatory pain
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DOI：
10.1152/ajpheart.00747.2005
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发表时间：
2006-02-01
影响因子：
4.8
通讯作者：
Davis, TP
中科院分区：
文献类型：
--
作者：
Huber, JD;Campos, CR;Davis, TP
吉梅尔-角叉菜胶诱导炎性疼痛后血脑屏障ICAM-1表达和脑小胶质细胞活化的改变美国生理学杂志心脏循环生理学290：H732-H740，2006年。首次发表于2005年9月30日; doi：10.1152/ajpheart.00747.2005。先前的研究表明，外周炎性疼痛增加血脑屏障（BBB）的通透性，改变紧密连接蛋白的表达和阿片类镇痛药向大脑的递送。目前尚不清楚的是外周炎症过程中哪些途径和介质影响BBB的功能和结构。本研究探讨了洋地黄-角叉菜胶诱导的炎性疼痛（CIP）对血脑屏障ICAM-1表达的影响。我们还研究了一些促炎细胞因子和小胶质细胞活化在大脑中的全身贡献，以阐明在CIP过程中参与BBB破坏的途径。我们研究ICAM-1的RNA和蛋白质表达水平在分离的大鼠脑微血管CIP后，使用RT-PCR和Western印迹分析，筛选炎症细胞因子在炎症的时间过程中，评估白色血细胞计数，并探测血脑屏障和中枢神经系统的刺激和白细胞迁移，使用免疫组织化学和流式细胞术。结果显示，CIP后ICAM-1 RNA和蛋白表达早期增加，而几种促炎细胞因子的循环水平没有变化。ICAM-1蛋白表达在48 h时有明显变化。免疫组化显示ICAM-1的诱导具有区域特异性，在丘脑、额叶和顶叶皮质中的表达增加，这与活化的小胶质细胞的表达增加直接相关。本研究的结果是CIP诱导BBB处ICAM-1 mRNA和蛋白表达增加，并且全身促炎介质在早期反应（1-6小时）中没有明显作用;然而，小胶质细胞活化的脑区域特异性增加表明中枢介导的反应的潜力。
Alterations in blood-brain barrier ICAM-1 expression and brain microglial activation after gimel-carrageenan-induced inflammatory pain. Am J Physiol Heart Circ Physiol 290: H732-H740, 2006. First published September 30, 2005; doi:10.1152/ajpheart.00747.2005.-Previous studies showed that peripheral inflammatory pain increased blood-brain barrier (BBB) permeability and altered tight junction protein expression and the delivery of opioid analgesics to the brain. What remains unknown is which pathways and mediators during peripheral inflammation affect BBB function and structure. The current study investigated effects of gimel-carrageenan-induced inflammatory pain (CIP) on BBB expression of ICAM-1. We also examined the systemic contribution of a number of proinflammatory cytokines and microglial activation in the brain to elucidate pathways involved in BBB disruption during CIP. We investigated ICAM-1 RNA and protein expression levels in isolated rat brain microvessels after CIP using RT-PCR and Western blot analyses, screened inflammatory cytokines during the time course of inflammation, assessed white blood cell counts, and probed for BBB and central nervous system stimulation and leukocyte transmigration using immunohistochemistry and flow cytometry. Results showed an early increase in ICAM-1 RNA and protein expression after CIP with no change in circulating levels of several proinflammatory cytokines. Changes in ICAM-1 protein expression were noted at 48 h. Immunohistochemistry showed that the induction of ICAM-1 was region specific with increased expression noted in the thalamus and frontal and parietal cortices, which directly correlated with increased expression of activated microglia. The findings of the present study were that CIP induces increased ICAM-1 mRNA and protein expression at the BBB and that systemic proinflammatory mediators play no apparent role in the early response (1-6 h); however, brain region-specific increases in microglial activation suggest a potential for a central-mediated response.