Long-term neuroblast migration along blood vessels in an area with transient angiogenesis and increased vascularization after stroke
Long-term neuroblast migration along blood vessels in an area with transient angiogenesis and increased vascularization after stroke
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DOI：
10.1161/strokeaha.107.488445
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发表时间：
2007-11-01
期刊：
影响因子：
8.3
通讯作者：
Lindvall, Olle
中科院分区：
文献类型：
--
作者：
Thored, Paer;Wood, James;Lindvall, Olle
背景与目的——大脑中动脉闭塞（MCAO）引起的卒中可导致脑室下区（SVZ）干细胞/祖细胞长期形成新的纹状体神经元。我们探讨了MCAO是否会导致同侧SVZ和邻近纹状体缺氧、血管密度变化和血管生成，并确定了神经母细胞迁移与血管系统的关系。方法：对成年大鼠进行2小时MCAO。在MCAO期间或6周后注射Hypoxyprobe-1观察缺氧情况。血管密度和长度用立体学估计。在MCAO后的第1、2周或第7、8周，用5‘-溴-2’脱氧尿苷（BrdU）标记新细胞，用BrdU抗体和内皮细胞标志物免疫组织化学方法评估血管生成情况。用共聚焦显微镜测量神经母细胞到最近血管的距离。结果：缺血性损伤引起短暂性缺氧和早期低级别血管生成，但未造成SVZ血管密度损伤或增加。在前2周内，在靠近SVZ的背内侧纹状体中检测到血管新生，血管化也持续增加。在MCAO后2、6和16周，大多数神经母细胞通过这一区域向与血管密切相关的损伤区迁移。结论-脉管系统在脑卒中后纹状体神经发生中起重要作用。在几个月的时间里，神经母细胞通过早期血管重塑和血管密度持续增加的区域向血管附近迁移。优化血管化应是促进脑卒中后神经发生和修复的重要策略。
Background and Purpose - Stroke induced by middle cerebral artery occlusion (MCAO) causes long-term formation of new striatal neurons from stem/progenitor cells in the subventricular zone (SVZ). We explored whether MCAO leads to hypoxia, changes in vessel density, and angiogenesis in the ipsilateral SVZ and adjacent striatum, and determined the relation between the migrating neuroblasts and the vasculature.Methods - Adult rats were subjected to 2 hours of MCAO. Hypoxia was studied by injecting Hypoxyprobe-1 during MCAO or 6 weeks later. Vessel density and length was estimated using stereology. New cells were labeled with 5'-bromo-2' deoxyuridine (BrdU) during weeks 1 and 2 or 7 and 8 after MCAO, and angiogenesis was assessed immunohistochemically with antibodies against BrdU and endothelial cell markers. Distance from neuroblasts to nearest vessel was measured using confocal microscopy.Results - The ischemic insult caused transient hypoxia and early, low-grade angiogenesis, but no damage or increase of vascular density in the SVZ. Angiogenesis was detected during the first 2 weeks in the dorsomedial striatum adjacent to the SVZ, which also showed long-lasting increase of vascularization. At 2, 6, and 16 weeks after MCAO, the majority of neuroblasts migrated through this area toward the damage, closely associated with blood vessels.Conclusions - The vasculature plays an important role for long-term striatal neurogenesis after stroke. During several months, neuroblasts migrate close to blood vessels through an area exhibiting early vascular remodeling and persistently increased vessel density. Optimizing vascularization should be an important strategy to promote neurogenesis and repair after stroke.