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Glia. 2019 Aug;67(8):1434-1448. doi: 10.1002/glia.23616. Epub 2019 Apr 5.

Microglial proliferation and monocyte infiltration contribute to microgliosis following status epilepticus.

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School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China.
Department of Cell Biology and Neuroscience, School of Arts and Sciences, Rutgers University, Piscataway, New Jersey.
Department of Neurology, Mayo Clinic, Rochester, Minnesota.
Department of Environmental Health Sciences, Robert Stempel School of Public Health and Social Work, Florida International University, Miami, Florida.
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida.
Department of Immunology, Mayo Clinic, Rochester, Minnesota.


Microglial activation has been recognized as a major contributor to inflammation of the epileptic brain. Seizures are commonly accompanied by remarkable microgliosis and loss of neurons. In this study, we utilize the CX3CR1GFP/+ CCR2RFP/+ genetic mouse model, in which CX3CR1+ resident microglia and CCR2+ monocytes are labeled with GFP and RFP, respectively. Using a combination of time-lapse two-photon imaging and whole-cell patch clamp recording, we determined the distinct morphological, dynamic, and electrophysiological characteristics of infiltrated monocytes and resident microglia, and the evolution of their behavior at different time points following kainic acid-induced seizures. Seizure activated microglia presented enlarged somas with less ramified processes, whereas, infiltrated monocytes were smaller, highly motile cells that lacked processes. Moreover, resident microglia, but not infiltrated monocytes, proliferate locally in the hippocampus after seizure. Microglial proliferation was dependent on the colony-stimulating factor 1 receptor (CSF-1R) pathway. Pharmacological inhibition of CSF-1R reduced seizure-induced microglial proliferation, which correlated with attenuation of neuronal death without altering acute seizure behaviors. Taken together, we demonstrated that proliferation of activated resident microglia contributes to neuronal death in the hippocampus via CSF-1R after status epilepticus, providing potential therapeutic targets for neuroprotection in epilepsy.


colony stimulating factor 1 receptor; epilepsy; infiltration; microglia; monocytes; proliferation

[Available on 2020-08-01]

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