Live imaging of astrocyte responses to acute injury reveals selective juxtavascular proliferation

Live imaging of astrocyte responses to acute injury reveals selective juxtavascular proliferation
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DOI:
10.1038/nn.3371
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发表时间:
2013-05-01
影响因子:
25
通讯作者:
Goetz, Magdalena
Goetz, Magdalena
中科院分区:
医学1区
文献类型:
--
作者:
Bardehle, Sophia;Krueger, Martin;Goetz, Magdalena

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星形胶质细胞被认为在脑损伤后具有重要作用,但它们的行为在很大程度上是从死后分析中推断出来的。为了研究将星形胶质细胞招募到损伤部位的机制,我们使用体内双光子激光扫描显微镜观察急性损伤后几周内成年小鼠大脑皮层中GFP标记的星形胶质细胞的反应。实时成像显示单个星形胶质细胞的反应具有显着的异质性,一个子集保留其初始形态,另一个子集将其过程导向病变,一个独特的子集位于血管旁部位增殖。虽然没有星形胶质细胞积极向损伤部位迁移,近血管星形胶质细胞的选择性增殖后,观察到一个病变的介绍,仍然是这种情况下,即使程度降低,星形胶质细胞特异性缺失的RhoGTdR Cdc42。因此,损伤后星形胶质细胞的募集仅依赖于特定小生境中的增殖。
Astrocytes are thought to have important roles after brain injury, but their behavior has largely been inferred from postmortem analysis. To examine the mechanisms that recruit astrocytes to sites of injury, we used in vivo two-photon laser-scanning microscopy to follow the response of GFP-labeled astrocytes in the adult mouse cerebral cortex over several weeks after acute injury. Live imaging revealed a marked heterogeneity in the reaction of individual astrocytes, with one subset retaining their initial morphology, another directing their processes toward the lesion, and a distinct subset located at juxtavascular sites proliferating. Although no astrocytes actively migrated toward the injury site, selective proliferation of juxtavascular astrocytes was observed after the introduction of a lesion and was still the case, even though the extent was reduced, after astrocyte-specific deletion of the RhoGTPase Cdc42. Thus, astrocyte recruitment after injury relies solely on proliferation in a specific niche.