Microglia play beneficial roles in multiple experimental seizure models

Microglia play beneficial roles in multiple experimental seizure models

Seizure disorders are common, affecting both the young and the old. Currently available antiseizure drugs are ineffective in a third of patients and have been developed with a focus on known neurocentric mechanisms, raising the need for investigations into alternative and complementary mechanisms th...

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Bibliographic Details
Published in:Glia Vol. 71; no. 7; pp. 1699 - 1714
Main Authors: Gibbs‐Shelton, Synphane, Benderoth, Jordan, Gaykema, Ronald P., Straub, Justyna, Okojie, Kenneth A., Uweru, Joseph O., Lentferink, Dennis H., Rajbanshi, Binita, Cowan, Maureen N., Patel, Brij, Campos‐Salazar, Anthony Brayan, Perez‐Reyes, Edward, Eyo, Ukpong B.
Format: Journal Article
Language:English
Published: Hoboken, USA John Wiley & Sons, Inc 01-07-2023
Wiley Subscription Services, Inc
Subjects:
Brain
Cell activation
Central nervous system
Convulsions & seizures
CSF1R
Epilepsy
Humans
Immune system
Immunosuppressive agents
Inflammation
kindling
Microglia
PLX3397
Seizures
Seizures - drug therapy
Side effects
PLX3397
CSF1R
seizures
inflammation
microglia
kindling
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Summary:Seizure disorders are common, affecting both the young and the old. Currently available antiseizure drugs are ineffective in a third of patients and have been developed with a focus on known neurocentric mechanisms, raising the need for investigations into alternative and complementary mechanisms that contribute to seizure generation or its containment. Neuroinflammation, broadly defined as the activation of immune cells and molecules in the central nervous system (CNS), has been proposed to facilitate seizure generation, although the specific cells involved in these processes remain inadequately understood. The role of microglia, the primary inflammation‐competent cells of the brain, is debated since previous studies were conducted using approaches that were less specific to microglia or had inherent confounds. Using a selective approach to target microglia without such side effects, we show a broadly beneficial role for microglia in limiting chemoconvulsive, electrical, and hyperthermic seizures and argue for a further understanding of microglial contributions to contain seizures. Main Points PLX3397 eliminates microglia but not peripheral immune cells. Microglial elimination with PLX3397 results in heightened seizures in 3 seizure models. Heightened seizures occur independent of cytokine levels in chemoconvulsive seizures.
ISSN:0894-1491
1098-1136
DOI:10.1002/glia.24364