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Brain. 2018 Dec 1;141(12):3343-3360. doi: 10.1093/brain/awy276.

Microglial phenotypes in the human epileptic temporal lobe.

Author information

1
Inserm U1127, CNRS UMR7225, Sorbonne Universités, UPMC Univ Paris 6 UMR S1127, Institut du Cerveau et de la Moelle épinière, Paris, France.
2
École normale supérieure, PSL Research University, CNRS, Inserm, Institut de Biologie de l'École normale supérieure (IBENS), Plateforme Génomique, Paris, France.
3
AP-HP, GH Pitie-Salpêtrière-Charles Foix, Epilepsy Unit (VN, MB, SD), Neuropathologie (FB), Neurochirurgie (BM, SC), Paris, France.

Abstract

Microglia, the immune cells of the brain, are highly plastic and possess multiple functional phenotypes. Differences in phenotype in different regions and different states of epileptic human brain have been little studied. Here we use transcriptomics, anatomy, imaging of living cells and ELISA measurements of cytokine release to examine microglia from patients with temporal lobe epilepsies. Two distinct microglial phenotypes were explored. First we asked how microglial phenotype differs between regions of high and low neuronal loss in the same brain. Second, we asked how microglial phenotype is changed by a recent seizure. In sclerotic areas with few neurons, microglia have an amoeboid rather than ramified shape, express activation markers and respond faster to purinergic stimuli. The repairing interleukin, IL-10, regulates the basal phenotype of microglia in the CA1 and CA3 regions with neuronal loss and gliosis. To understand changes in phenotype induced by a seizure, we estimated the delay from the last seizure until tissue collection from changes in reads for immediate early gene transcripts. Pseudotime ordering of these data was validated by comparison with results from kainate-treated mice. It revealed a local and transient phenotype in which microglia secrete the human interleukin CXCL8, IL-1B and other cytokines. This secretory response is mediated in part via the NRLP3 inflammasome.

PMID:
30462183
PMCID:
PMC6277010
[Available on 2019-06-01]
DOI:
10.1093/brain/awy276

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