Characterization of monocyte chemoattractant protein-1 expression following a kainate model of status epilepticus

Characterization of monocyte chemoattractant protein-1 expression following a kainate model of status epilepticus
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DOI:
10.1016/j.brainres.2007.08.092
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发表时间:
2007-11-28
期刊:
影响因子:
2.9
通讯作者:
Sapolsky, Robert M.
Sapolsky, Robert M.
中科院分区:
医学3区
文献类型:
--
作者:
Manley, Nathan C.;Bertrand, Anthony A.;Sapolsky, Robert M.

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癫痫发作引起的脑损伤诱导了涉及多种因素的强烈炎症反应。尽管趋化因子的表达已被确定为这种反应的一部分,但关于其对癫痫发病机制的相对贡献仍存在疑问。为了解决这个问题,我们报告的表达谱的趋化因子,单核细胞趋化蛋白-1(MCP-1,CCL 2),在红藻氨酸诱导的癫痫发作在大鼠海马。此外,我们比较了MCP-1表达的时间分布的血脑屏障(BBB)的通透性和免疫细胞在损伤部位的招聘,因为这两个事件都与MCP-1。我们发现,血脑屏障通透性增加之前,MCP-1的上调,而MCP-1的上调和免疫细胞募集同时发生,7-13小时后开放的血脑屏障。我们的研究结果支持以下结论:(1)血脑屏障向大蛋白开放不需要MCP-1上调;(2)白细胞迁移不足以诱导血脑屏障向大蛋白开放;(3)MCP-1上调可能介导癫痫损伤期间巨噬细胞/小胶质细胞和粒细胞的募集,从而避免了对该趋化因子的进一步研究。(C)2007 Elsevier B. V.保留所有权利。
Brain injury due to seizure induces a robust inflammatory response that involves multiple factors. Although the expression of chemokines has been identified as a part of this response, there are remaining questions about their relative contribution to seizure pathogenesis. To address this, we report the expression profile of the chemokine, monocyte chemoattractant protein-1 (MCP-1, CCL2), during kainate-induced seizure in the rat hippocampus. Furthermore, we compare MCP-1 expression to the temporal profile of blood-brain barrier (BBB) permeability and immune cell recruitment at the injury site, since both of these events have been linked to MCP-1. We find that BBB permeability increased prior to upregulation of MCP-1, while MCP-1 upregulation and immune cell recruitment occurred concurrently, 7-13 h after opening of the BBB. Our findings support the following conclusions: (1) BBB opening to large proteins does not require MCP-1 upregulation; (2) Leukocyte immigration is not sufficient to induce BBB opening to large proteins; (3) MCP-1 upregulation likely mediates recruitment of macrophages/microglia and granulocytes during seizure injury, thus warranting further investigation of this chemokine. (C) 2007 Elsevier B.V. All rights reserved.