Department of Neurosurgery, University of Michigan, Ann Arbor.
Stroke. 2022 Nov;53(11):e472-e476. doi: 10.1161/STROKEAHA.122.040302. Epub 2022 Sep 23.
Microglia are important brain immune cells. However, it is difficult to differentiate microglia from monocyte-derived macrophages. To visualize microglia changes following intracerebral hemorrhage (ICH), we utilized a genetic knock-in mouse line, Tmem119 (transmembrane protein 119)-EGFP (enhanced green fluorescent protein), which expresses EGFP specifically in microglia.
There were 2 parts in this study. First, autologous blood was injected into the right basal ganglia to model ICH in Tmem119-EGFP mice. Mice were euthanized at 4 hours, days 1, 3, and 7 after ICH. Sham animals were used as controls. Second, Tmem119-EGFP mice were injected with iron or thrombin, factors involved in ICH-induced injury, and were euthanized at 4 hours. Naïve mice were controls. Brains were harvested for histology.
The number of perihematomal microglia significantly decreased 1 day after ICH, but markedly increased by days 3 and 7. Microglia death was also induced by intracerebral iron injection while microglia proliferation was found with intracerebral thrombin injection.
Perihematomal microglia death and proliferation after ICH are visualized in vivo with a Tmem119-EGFP transgenic mouse line. Iron and thrombin may contribute to ICH-induced microglia death and proliferation, respectively.
小胶质细胞是大脑中重要的免疫细胞。然而，要将小胶质细胞与单核细胞衍生的巨噬细胞区分开来却很困难。为了可视化脑出血（ICH）后小胶质细胞的变化，我们利用了一种基因敲入小鼠系，Tmem119（跨膜蛋白 119）-EGFP（增强型绿色荧光蛋白），该基因在小胶质细胞中特异性表达 EGFP。
本研究包括两个部分。首先，将自体血液注入右侧基底节以在 Tmem119-EGFP 小鼠中建立 ICH 模型。ICH 后 4 小时、第 1 天、第 3 天和第 7 天处死小鼠。假手术动物作为对照。其次，向 Tmem119-EGFP 小鼠注射铁或凝血酶，这两种因子都参与 ICH 诱导的损伤，然后在 4 小时处死。未处理的小鼠作为对照。采集大脑进行组织学研究。
ICH 后 1 天，血肿周围的小胶质细胞数量明显减少，但在第 3 天和第 7 天显著增加。脑内铁注射也会诱导小胶质细胞死亡，而脑内凝血酶注射则会引起小胶质细胞增殖。
使用 Tmem119-EGFP 转基因小鼠系可以在体内可视化 ICH 后血肿周围的小胶质细胞死亡和增殖。铁和凝血酶可能分别导致 ICH 诱导的小胶质细胞死亡和增殖。
