Microglial proliferation and monocyte infiltration contribute to microgliosis following status epilepticus

Lijie Feng, Madhuvika Murugan, Dale B. Bosco, Yong Liu, Jiyun Peng, Gregory Alan Worrell, Hai Long Wang, Lauren E. Ta, Jason R. Richardson, Yuxian Shen, LongJun Wu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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 CX3CR1 GFP/+ CCR2 RFP/+ 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.

Original languageEnglish (US)
JournalGlia
DOIs
StatePublished - Jan 1 2019

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Status Epilepticus
Microglia
Monocytes
Seizures
Colony-Stimulating Factor Receptors
Macrophage Colony-Stimulating Factor
Hippocampus
Kainic Acid
Genetic Models
Carisoprodol
Encephalitis
Photons
Epilepsy
Pharmacology
Neurons

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Microglial proliferation and monocyte infiltration contribute to microgliosis following status epilepticus. / Feng, Lijie; Murugan, Madhuvika; Bosco, Dale B.; Liu, Yong; Peng, Jiyun; Worrell, Gregory Alan; Wang, Hai Long; Ta, Lauren E.; Richardson, Jason R.; Shen, Yuxian; Wu, LongJun.

In: Glia, 01.01.2019.

Research output: Contribution to journalArticle

Feng, Lijie ; Murugan, Madhuvika ; Bosco, Dale B. ; Liu, Yong ; Peng, Jiyun ; Worrell, Gregory Alan ; Wang, Hai Long ; Ta, Lauren E. ; Richardson, Jason R. ; Shen, Yuxian ; Wu, LongJun. / Microglial proliferation and monocyte infiltration contribute to microgliosis following status epilepticus. In: Glia. 2019.
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