In bacterial meningitis cortical brain damage is associated with changes in parenchymal MMP-9/TIMP-1 ratio and increased collagen type IV degradation
In bacterial meningitis cortical brain damage is associated with changes in parenchymal MMP-9/TIMP-1 ratio and increased collagen type IV degradation
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DOI：
10.1016/j.nbd.2005.09.007
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发表时间：
2006-03-01
影响因子：
6.1
通讯作者：
Leib, SL
中科院分区：
文献类型：
--
作者：
Sellner, J;Leib, SL
细菌性脑膜炎的不良结局与血脑屏障（BBB）的破坏有关。基质金属蛋白酶（MMPs）通过降解血脑屏障成分促进这一过程。这反过来导致细菌性脑膜炎的急性并发症，包括水肿形成、颅内压升高和随后的缺血。在肺炎球菌性脑膜炎的幼鼠模型中，我们测定了MMP-9和TIMP-1 （MMP的组织抑制剂）的实质平衡以及血脑屏障的结构完整性与皮质损伤的关系。数据表明，皮质损伤程度与实质明胶溶解活性和IV型胶原降解显著相关。明胶溶解增加与脑实质MMP-9/TIMP-1失衡有关。这些发现支持了MMPs介导的血脑屏障破坏有助于细菌性脑膜炎发病机制的概念，并且血管单位的保护可能具有神经保护潜力。(C) 2005爱思唯尔公司版权所有。
Adverse outcome in bacterial meningitis is associated with the breakdown of the blood-brain barrier (BBB). Matrix-metalloproteinases (MMPs) facilitate this process by degradation of components of the BBB. This in turn results in acute complications of bacterial meningitis including edema formation, increased intracranial pressure and subsequent ischemia. We determined the parenchymal balance of MMP-9 and TIMP-1 (tissue inhibitor of MMP) and the structural integrity of the BBB in relation to cortical damage in an infant rat model of pneumococcal meningitis. The data demonstrate that the extent of cortical damage is significantly associated with parenchymal gelatinolytic activity and collagen type IV degradation. The increased gelatinolysis was found to be associated with a brain parenchymal imbalance of MMP-9/TIMP-1. These findings provide support to the concept that MMPs mediated disruption of the BBB contributes to the pathogenesis of bacterial meningitis and that protection of the vascular unit may have neuroprotective potential. (C) 2005 Elsevier Inc. All rights reserved.