Blood-brain barrier tight junctions are altered during a 72-h exposure to λ-carrageenan-induced inflammatory pain
Blood-brain barrier tight junctions are altered during a 72-h exposure to λ-carrageenan-induced inflammatory pain
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DOI：
10.1152/ajpheart.00027.2002
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发表时间：
2002-10-01
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;Hau, VS;Davis, TP
在这项研究中，我们研究了lambda- carragean诱导的炎症性疼痛在72小时内对大鼠血脑屏障（BBB）功能和结构特性的影响。雌性Sprague-Dawley大鼠右后爪足底注射3% λ -卡拉胶诱导全身炎症反应。在1、3、6、12、24、48和72小时进行脑原位灌注和Western blot分析。脑原位灌注显示，与对照组相比，λ -卡拉胶在1、3、6和48小时显著增加了[C-14]蔗糖的脑摄取（分别为139 +/- 9%、166 +/- 19%、138 +/- 13%和146 +/- 7%）。毛细管耗竭分析证实脑摄取增加是由于血脑屏障通透性增加，而不是血管捕获。在离体脑微血管上进行封闭带蛋白-1 （ZO-1）和occludin的Western blot分析。ZO-1的表达在1、3和6小时显著增加，并在12小时后恢复到对照表达水平。总occludin的表达在1、3、6、12和48小时显著降低。该研究表明，lambda- carragean诱导的炎症性疼痛引起血脑屏障通透性的双期增加，第一阶段发生在1-6小时，第二阶段发生在48小时。血脑屏障功能的改变与occludin和ZO-1紧密连接蛋白表达的改变有关。紧密连接结构的改变可能对中枢神经系统稳态和治疗性药物传递具有重要的临床意义。
In this study, we examined the effect of lambda-carrageenan-induced inflammatory pain on the functional and structural properties of the rat blood-brain barrier (BBB) over a 72-h time period. Systemic inflammation was induced by an intraplantar injection of 3% lambda-carrageenan into the right hind paw of female Sprague-Dawley rats. In situ brain perfusion and Western blot analyses were performed at 1, 3, 6, 12, 24, 48, and 72 h. In situ brain perfusion showed lambda-carrageenan significantly increased brain uptake of [C-14] sucrose at 1, 3, 6, and 48 h (139 +/- 9%, 166 +/- 19%, 138 +/- 13%, and 146 +/- 7% compared with control, respectively). Capillary depletion analysis insured the increased brain uptake was due to increased BBB permeability and not vascular trapping. Western blot analyses for zonula occludens-1 (ZO-1) and occludin were performed on isolated cerebral microvessels. ZO-1 expression was significantly increased at 1, 3, and 6 h and returned to control expression levels by 12 h. Total occludin expression was significantly reduced at 1, 3, 6, 12, and 48 h. This investigation demonstrated that lambda-carrageenan-induced inflammatory pain elicits a biphasic increase in BBB permeability with the first phase occurring from 1-6 h and the second phase occuring at 48 h. Furthermore, changes in BBB function are correlated with altered tight junctional protein expression of occludin and ZO-1. Changes in the structure of tight junctions may have important clinical ramifications concerning central nervous system homeostasis and therapeutic drug delivery.