Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke.
Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke.
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DOI：
10.1038/ncomms11499
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发表时间：
2016-05-03
影响因子：
16.6
通讯作者：
Dénes Á
中科院分区：
文献类型：
--
作者：
Szalay G;Martinecz B;Lénárt N;Környei Z;Orsolits B;Judák L;Császár E;Fekete R;West BL;Katona G;Rózsa B;Dénes Á
小胶质细胞是大脑的主要免疫细胞，并有助于常见的脑部疾病。然而，目前还不清楚小胶质细胞如何影响体内受损脑中的神经元活性和存活。在这里，我们开发了一个精确控制的模型，脑缺血引起的脑损伤结合快速在体内双光子钙成像和选择性小胶质细胞操作。我们发现，选择性消除小胶质细胞导致了一个惊人的，60%的梗死面积增加，这是逆转的小胶质细胞再增殖。小胶质细胞介导的保护包括减少兴奋性毒性损伤，因为小胶质细胞的缺乏导致神经元钙反应失调、钙超载和神经元死亡增加。此外，在没有小胶质细胞的情况下，扩散去极化（SD）的发生率显著降低。因此，小胶质细胞参与体内脑损伤后神经元网络活动和SD的变化，这可能对常见的脑疾病具有重要意义。 小胶质细胞如何促进脑损伤或修复尚不清楚。在这里结合小胶质细胞操作和钙成像，作者表明，选择性消除小胶质细胞导致破坏神经元钙动力学和脑缺血后脑损伤显着增加。
Microglia are the main immune cells of the brain and contribute to common brain diseases. However, it is unclear how microglia influence neuronal activity and survival in the injured brain in vivo. Here we develop a precisely controlled model of brain injury induced by cerebral ischaemia combined with fast in vivo two-photon calcium imaging and selective microglial manipulation. We show that selective elimination of microglia leads to a striking, 60% increase in infarct size, which is reversed by microglial repopulation. Microglia-mediated protection includes reduction of excitotoxic injury, since an absence of microglia leads to dysregulated neuronal calcium responses, calcium overload and increased neuronal death. Furthermore, the incidence of spreading depolarization (SD) is markedly reduced in the absence of microglia. Thus, microglia are involved in changes in neuronal network activity and SD after brain injury in vivo that could have important implications for common brain diseases. How microglia contribute to brain injury or repair is unclear. Here combining microglia manipulations and calcium imaging, the authors show that selective elimination of microglia leads to disrupted neuronal calcium dynamics and markedly increased brain injury after cerebral ischemia.