Detachment of Brain Pericytes from the Basal Lamina is Involved in Disruption of the Blood-Brain Barrier Caused by Lipopolysaccharide-Induced Sepsis in Mice
Detachment of Brain Pericytes from the Basal Lamina is Involved in Disruption of the Blood-Brain Barrier Caused by Lipopolysaccharide-Induced Sepsis in Mice
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DOI：
10.1007/s10571-008-9322-x
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发表时间：
2009-05-01
影响因子：
4
通讯作者：
Kataoka, Yasufumi
中科院分区：
文献类型：
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作者：
Nishioku, Tsuyoshi;Dohgu, Shinya;Kataoka, Yasufumi
血脑屏障（BBB）高度限制了血液和中枢神经系统之间物质的运输。脑周细胞是血脑屏障的重要细胞成分之一，是位于微血管基底层的多功能、多形性细胞。本研究旨在通过脂多糖（LPS）诱导的小鼠脓毒性脑病模型来评估周细胞在血脑屏障破坏中的介导作用。将ICR小鼠腹腔注射LPS或生理盐水，并于注射后1、3、6和24 h处死。LPS注射后海马荧光素钠随时间积累；纤维蛋白原外渗的检测证实了这种高渗透性。注射LPS后小胶质细胞被激活，小胶质细胞数量随时间增加而增加。LPS处理小鼠在注射后6-24小时出现基底膜断裂和周细胞脱离。脂多糖处理小鼠的周细胞和基板单元的紊乱与小胶质细胞活化增加和脑血管通透性增加密切相关。这些发现表明，周细胞脱离和小胶质细胞激活可能参与了脑损伤中炎症反应引起的血脑屏障破坏的调解。
The blood-brain barrier (BBB) is highly restrictive of the transport of substances between blood and the central nervous system. Brain pericytes are one of the important cellular constituents of the BBB and are multifunctional, polymorphic cells that lie within the microvessel basal lamina. The present study aimed to evaluate the role of pericytes in the mediation of BBB disruption using a lipopolysaccharide (LPS)-induced model of septic encephalopathy in mice. ICR mice were injected intraperitoneally with LPS or saline and were sacrificed at 1, 3, 6, and 24 h after injection. Sodium fluorescein accumulated with time in the hippocampus after LPS injection; this hyperpermeability was supported by detecting the extravasation of fibrinogen. Microglia were activated and the number of microglia increased with time after LPS injection. LPS-treated mice exhibited a broken basal lamina and pericyte detachment from the basal lamina at 6-24 h after LPS injection. The disorganization in the pericyte and basal lamina unit was well correlated with increased microglial activation and increased cerebrovascular permeability in LPS-treated mice. These findings suggest that pericyte detachment and microglial activation may be involved in the mediation of BBB disruption due to inflammatory responses in the damaged brain.