Juxtavascular microglia migrate along brain microvessels following activation during early postnatal development
Juxtavascular microglia migrate along brain microvessels following activation during early postnatal development
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DOI：
10.1002/glia.10031
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发表时间：
2002-03-01
期刊：
影响因子：
6.2
通讯作者：
Dailey, ME
中科院分区：
文献类型：
--
作者：
Grossmann, R;Stence, N;Dailey, ME
哺乳动物脑组织中的一些实质小胶质细胞，被称为“血管旁小胶质细胞”，直接与血管的基底层接触；然而，这种独特的结构关系的功能后果尚不清楚。本研究采用创伤性脑损伤大鼠脑切片模型，研究血管旁小胶质细胞激活后的动态行为。通过荧光凝集素（FITC-IB4）染色的组织切片共聚焦3D重建鉴定血管旁小胶质细胞，该荧光凝集素可标记小胶质细胞和血管内皮细胞。免疫标记证实血管旁细胞是真正的实质小胶质细胞(OX42(+), ED2(-))，而不是血管周围细胞或周细胞。活体组织切片延时成像显示，激活的血管旁小胶质细胞撤回了大部分现存分支，但通常保持与血管的接触，通常在1-4小时内移动到血管表面。随后，一些小胶质细胞沿着血管实质表面移动，移动速度高达40 μ m/h。激活的血管旁小胶质细胞有时会反复向周围组织延伸面纱样突起，这与组织监视的作用一致。在体外培养10小时后，血管旁细胞的运动能力是非血管旁细胞的两倍，这表明血管旁细胞的激活反应增强。此外，38%的血管旁细胞沿血管迁移，而在非血管旁细胞中从未观察到这种情况。这些观察结果确定了一个移动的小胶质细胞亚群（10%-30%），它们在脑组织损伤后迅速激活并优先被招募到血管表面。小胶质细胞与脑微血管的动态和持续相互作用可能促进损伤脑实质与血脑屏障成分或血液循环免疫细胞之间的信号传导。(C) 2002 Wiley-Liss, Inc。
Some parenchymal microglia in mammalian brain tissues, termed ''juxtavascular microglia,'' directly contact the basal lamina of blood vessels; however, the functional consequences of this unique structural relationship are unknown. Here we used a rat brain slice model of traumatic brain injury to investigate the dynamic behavior of juxtavascular microglia following activation. Juxtavascular microglia were identified by confocal 3D reconstruction in tissue slices stained with a fluorescent lectin (FITC-IB4) that labels both microglia and blood vessel endothelial cells. Immunolabeling confirmed that juxtavascular cells were true parenchymal microglia (OX42(+), ED2(-)) and not perivascular cells or pericytes. Time-lapse imaging in live tissue slices revealed that activating juxtavascular microglia withdraw most extant branches but often maintain contact with blood vessels, usually moving to the surface of a vessel within 1-4 h. Subsequently, some microglia migrate along the parenchymal surface of vessels, moving at rates up to 40 mum/h. Activated juxtavascular microglia sometimes repeatedly extend veil-like protrusions into the surrounding tissue, consistent with a role in tissue surveillance. Juxtavascular cells were twice as likely as nonjuxtavascular cells to be locomotory by 10 h in vitro, suggesting an enhanced activation response. Moreover, 38% of all juxtavascular cells migrated along a vessel, whereas this was never observed for a nonjuxtavascular cell. These observations identify a mobile subpopulation (10%-30%) of parenchymal microglia that activate rapidly and are preferentially recruited to the surfaces of blood vessels following brain tissue injury. The dynamic and sustained interaction of microglia with brain microvessels may facilitate signaling between injured brain parenchyma and components of the blood-brain barrier or circulating immune cells of the blood in vivo. (C) 2002 Wiley-Liss, Inc.