Colony stimulating factor 1 receptor inhibition eliminates microglia and attenuates brain injury after intracerebral hemorrhage.
Colony stimulating factor 1 receptor inhibition eliminates microglia and attenuates brain injury after intracerebral hemorrhage.
复制标题
集落刺激因子 1 受体抑制可消除小胶质细胞并减轻脑出血后的脑损伤
DOI：
10.1177/0271678x16666551
复制
发表时间：
2017-07
期刊：
影响因子：
--
通讯作者：
Shi FD
中科院分区：
文献类型：
--
作者：
Li M;Li Z;Ren H;Jin WN;Wood K;Liu Q;Sheth KN;Shi FD
小胶质细胞是脑出血的第一反应者，但其在脑出血中的确切作用仍有待确定。小胶质细胞是表达集落刺激因子1受体的唯一类型的脑细胞，集落刺激因子1受体是髓系细胞的关键调节因子。在这里，我们确定了一种集落刺激因子1受体抑制剂（PLX3397）对小胶质细胞的影响，并在实验性小鼠脑出血的背景下的结果。我们表明，PLX3397有效地耗尽小胶质细胞，并在脑出血后持续耗尽小胶质细胞。重要的是，在两种注射胶原酶或自体血诱导的脑出血实验模型中，抑制集落刺激因子1受体可减轻神经缺损和脑水肿。集落刺激因子1受体抑制的益处与脑出血后脑内白细胞浸润减少和血脑屏障完整性改善相关，并且每个观察结果与病灶大小或血肿体积无关。这些结果表明，抑制集落刺激因子1受体信号消融小胶质细胞，并赋予脑出血后的保护。
Microglia are the first responders to intracerebral hemorrhage, but their precise role in intracerebral hemorrhage remains to be defined. Microglia are the only type of brain cells expressing the colony-stimulating factor 1 receptor, a key regulator for myeloid lineage cells. Here, we determined the effects of a colony-stimulating factor 1 receptor inhibitor (PLX3397) on microglia and the outcome in the context of experimental mouse intracerebral hemorrhage. We show that PLX3397 effectively depleted microglia, and the depletion of microglia was sustained after intracerebral hemorrhage. Importantly, colony-stimulating factor 1 receptor inhibition attenuated neurodeficits and brain edema in two experimental models of intracerebral hemorrhage induced by injection of collagenase or autologous blood. The benefit of colony-stimulating factor 1 receptor inhibition was associated with reduced leukocyte infiltration in the brain and improved blood–brain barrier integrity after intracerebral hemorrhage, and each observation was independent of lesion size or hematoma volume. These results demonstrate that suppression of colony-stimulating factor 1 receptor signaling ablates microglia and confers protection after intracerebral hemorrhage.