Long-Term Accumulation of Microglia with Proneurogenic Phenotype Concomitant with Persistent Neurogenesis in Adult Subventricular Zone After Stroke
Long-Term Accumulation of Microglia with Proneurogenic Phenotype Concomitant with Persistent Neurogenesis in Adult Subventricular Zone After Stroke
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DOI：
10.1002/glia.20810
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发表时间：
2009-06-01
期刊：
影响因子：
6.2
通讯作者：
Lindvall, Olle
中科院分区：
文献类型：
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作者：
Thored, Par;Heldmann, Ursula;Lindvall, Olle
成年大鼠室下区(SVZ)的神经干细胞(NSCs)在缺血性卒中后的几个月内产生新的纹状体神经元。与缺血损伤相关的小胶质细胞反应是否延伸到SVZ并影响神经母细胞的产生尚不清楚。在这里，我们展示了在大鼠大脑中动脉闭塞2小时后，同侧SVZ内激活的小胶质细胞数量增加，并伴随着神经母细胞迁移到纹状体，在2、6和16周达到最大值。在梗死区周围纹状体，激活的小胶质细胞数量在2周时已达到峰值，此后下降。SVZ内的小胶质细胞存在于或来源于骨髓，在损伤后2周达到最大增殖。在SVZ，小胶质细胞呈分支或中等形态，表明炎症状态下调，而梗死区周围纹状体内常见阿米巴样或圆形吞噬小胶质细胞。SVZ中表达抗原提呈细胞标志物(MHC-II、CD86)的小胶质细胞数量增多，但检测到的淋巴细胞很少。用定量聚合酶链式反应检测到SVZ组织中胰岛素样生长因子-1(IGF-1)基因的表达在短期和长期(梗死后1周和6周)均显著增加。卒中后2周、6周和16周，SVZ内表达IGF-1的小胶质细胞数量增加。16周时，SVZ内5%的小胶质细胞表达IGF-1蛋白，但未见其他细胞表达IGF-1蛋白，可减轻NSCs的凋亡，促进其增殖和分化。SVZ内长期积聚的具有神经源性表型的小胶质细胞提示，这些细胞对卒中后持续的神经再生具有支持作用。(C)2008年Wiley-Liss，Inc.
Neural stem cells (NSCs) in the adult rat subventricular zone (SVZ) generate new striatal neurons during several months after ischemic stroke. Whether the microglial response associated with ischemic injury extends into SVZ and influences neuroblast production is unknown. Here, we demonstrate increased numbers of activated microglia in ipsilateral SVZ concomitant with neuroblast migration into the striatum at 2, 6, and 16 weeks, with maximum at 6 weeks, following 2 h middle cerebral artery occlusion in rats. In the peri-infarct striatum, numbers of activated microglia peaked already at 2 weeks and declined thereafter. Microglia in SVZ were resident or originated from bone marrow, with maximum proliferation during the first 2 weeks postinsult. In SVZ, microglia exhibited ramified or intermediate morphology, signifying a downregulated inflammatory profile, whereas amoeboid or round phagocytic microglia were frequent in the peri-infarct striatum. Numbers of microglia expressing markers of antigen-presenting cells (MHC-II, CD86) increased in SVZ but very few lymphocytes were detected. Using quantitative PCR, strong short- and long-term increase (at 1 and 6 weeks postinfarct) of insulin-like growth factor-1 (IGF-1) gene expression was detected in SVZ tissue. Elevated numbers of IGF-1-expressing microglia were found in SVZ at 2, 6, and 16 weeks after stroke. At 16 weeks, 5% of microglia but no other cells in SVZ expressed the IGF-1 protein, which mitigates apoptosis and promotes proliferation and differentiation of NSCs. The long-term accumulation of microglia with proneurogenic phenotype in the SVZ implies a supportive role of these cells for the continuous neurogenesis after stroke. (C) 2008 Wiley-Liss, Inc.