期刊
BRAIN BEHAVIOR AND IMMUNITY
卷 89, 期 -, 页码 245-255出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2020.06.028
关键词
Microglia; Microglia depletion; Microglia repopulation; Kainic acid; Epilepsy; Status epilepticus; Spontaneous recurrent seizures; Neuronal degeneration
资金
- National Institute of Health [R01NS088627, R01NS112144]
Microglia are the resident immune cells of the center nervous system and participate in various neurological diseases. Here we determined the function of microglia in epileptogenesis using microglial ablation approaches. Three different microglia-specific genetic tools were used, CX3CR1(CreER/+):R26(iDTA/+), CX3CR1(CreER/+):R26(iDTR/+), and CX3CR1(CreER/+):Csf1r(Flox/Flox) mice. We found that microglial depletion led to worse kainic acid (KA)induced status epilepticus, higher mortality rate, and increased neuronal degeneration in the hippocampus. In KA-induced chronic spontaneous recurrent seizures, microglial depletion increased seizure frequency, interictal spiking, and seizure duration. Therefore, microglial depletion aggravates the severity of KA-induced acute and chronic seizures. Interestingly, microglial repopulation reversed the effects of depletion upon KA-induced status epilepticus. Our results demonstrate a beneficial role of microglia in suppressing both acute and chronic seizures, suggesting that microglia are a potential therapeutic target for the management of epilepsy.
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