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Updated: Mar 21, 2026

Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after
Gergely Szalay1, Bernadett Martinecz2, Nikolett Lénárt2
1Two-Photon Imaging Center, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony U. 43, Budapest 1083, Hungary.
Abstract:
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.
Insights
Microglia, the brain's immune cells, protect against brain injury by reducing excitotoxic damage and neuronal death. Their absence worsens stroke outcomes, highlighting their crucial role in brain health.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Microglia are the primary immune cells in the brain.
- Their role in neuronal activity and survival following brain injury in vivo remains unclear.
- Microglia are implicated in various common brain diseases.
Purpose of the Study:
- To investigate the influence of microglia on neuronal activity and survival in a mouse model of cerebral ischemia.
- To elucidate the protective mechanisms of microglia in the context of brain injury.
Main Methods:
- Development of a controlled model of cerebral ischemia in vivo.
- Utilized fast in vivo two-photon calcium imaging.
- Employed selective microglial manipulation (elimination and repopulation).
Main Results:
- Selective elimination of microglia increased infarct size by 60%.
- Microglial absence led to dysregulated neuronal calcium responses, calcium overload, and increased neuronal death.
- The incidence of spreading depolarization (SD) was significantly reduced in the absence of microglia.
Conclusions:
- Microglia play a critical protective role in mitigating neuronal damage after cerebral ischemia.
- Microglia modulate neuronal network activity and spreading depolarization following brain injury.
- These findings have significant implications for understanding and treating common brain diseases involving brain injury.
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