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Published on: August 7, 2020
Novel Approach to Visualize Microglia Death and Proliferation After Intracerebral Hemorrhage in Mice
Fenghui Ye1, Jinting Yang1, Ya Hua1
1Department of Neurosurgery, University of Michigan, Ann Arbor.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Intracerebral hemorrhage (ICH) causes microglia death and proliferation, visualized using Tmem119-EGFP mice. Iron and thrombin may drive these distinct microglia responses after brain injury.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are crucial brain immune cells, but distinguishing them from macrophages is challenging.
- Visualizing microglia dynamics after intracerebral hemorrhage (ICH) is essential for understanding brain injury.
- A Tmem119-EGFP transgenic mouse line allows specific visualization of microglia.
Purpose of the Study:
- To visualize and characterize microglia alterations in response to ICH.
- To investigate the roles of iron and thrombin in ICH-induced microglia changes.
Main Methods:
- Modeled ICH by injecting autologous blood into Tmem119-EGFP mice, assessing microglia at multiple time points.
- Injected iron or thrombin into Tmem119-EGFP mice to study their specific effects on microglia.
- Utilized histology to analyze brain tissue from control and experimental groups.
Main Results:
- Perihematomal microglia numbers decreased at 1 day post-ICH but increased significantly by days 3 and 7.
- Intracerebral iron injection induced microglia death.
- Intracerebral thrombin injection promoted microglia proliferation.
Conclusions:
- The Tmem119-EGFP mouse line effectively visualizes in vivo microglia death and proliferation following ICH.
- Iron and thrombin are implicated as potential contributors to microglia death and proliferation, respectively, after ICH.
