Angiogenesis after stroke is correlated with increased numbers of macrophages: The clean-up hypothesis
Angiogenesis after stroke is correlated with increased numbers of macrophages: The clean-up hypothesis
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DOI：
10.1097/00004647-200110000-00011
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发表时间：
2001-10-01
影响因子：
6.3
通讯作者：
Lyden, PD
中科院分区：
文献类型：
--
作者：
Manoonkitiwongsa, PS;Jackson-Friedman, C;Lyden, PD
局灶性脑缺血后，脑细胞会产生并分泌血管生成肽，但这种血管生成反应的目的尚不清楚。由于最大可能的局部脑血流量是由单位体积内微血管的数量决定的，因此有可能分泌血管生成肽以产生新的侧支通道；其他可能性包括神经保护、恢复/再生和清除坏死碎片。如果大脑试图产生新的侧支循环，则缺血后微血管密度应显着增加。相反，如果血管生成信号分子有其他用途，微血管密度可能会略有增加或根本不增加。为了澄清这一点，作者用定量形态测量法测量了微血管密度。成年雄性 Sprague-Dawley 大鼠的左大脑中动脉用管腔内尼龙缝合线闭塞 4 小时，然后再灌注 7、14、19 或 30 天。对照组未接受手术或缝线闭合。使用半自动立体学方法通过光学显微镜形态测量法测量微血管密度和巨噬细胞数量的变化。微血管密度仅在邻近全坏死区域的缺血边缘增加，并且总是与巨噬细胞数量增加相关。与正常动物相比，没有巨噬细胞的缺血性大脑区域没有表现出血管分布变化。这些数据表明，缺血诱导的微血管的形成有利于巨噬细胞的浸润和坏死脑的清除。
Brain cells manufacture and secrete angiogenic peptides after focal cerebral ischemia, but the purpose of this angiogenic response is unknown. Because the maximum possible regional cerebral blood flow is determined by the quantity of microvessels in each unit volume, it is possible that angiogenic peptides are secreted to generate new collateral channels; other possibilities include neuroprotection, recovery/regeneration, and removal of necrotic debris. If the brain attempts to create new collaterals, microvessel density should increase significantly after ischemia. Conversely, if angiogenic-signaling molecules serve some other purpose, microvessel densities may increase slightly or not at all. To clarify, the authors measured microvessel densities with quantitative morphometry. Left middle cerebral arteries of adult male Sprague-Dawley rats were occluded with intraluminal nylon suture for 4 hours followed by 7, 14, 19, or 30 days of reperfusion. Controls received no surgery or suture occlusion. Changes in microvessel density and macrophage numbers were measured by light microscopic morphometry using semiautomated stereologic methods. Microvessel density increased only in the ischemic margin adjacent to areas of pannecrosis and was always associated with increased numbers of macrophages. Ischemic brain areas without macrophages displayed no vascularity changes compared with normal animals. These data suggest that ischemia-induced microvessels are formed to facilitate macrophage infiltration and removal of necrotic brain.