Microglial depletion aggravates the severity of acute and chronic seizures in mice

Brain Behav Immun. 2020 Oct;89:245-255. doi: 10.1016/j.bbi.2020.06.028. Epub 2020 Jul 2.

Abstract

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, CX3CR1CreER/+:R26iDTA/+, CX3CR1CreER/+:R26iDTR/+, and CX3CR1CreER/+:Csf1rFlox/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.

Keywords: Epilepsy; Kainic acid; Microglia; Microglia depletion; Microglia repopulation; Neuronal degeneration; Spontaneous recurrent seizures; Status epilepticus.

Publication types

  • Research Support, N.I.H., Extramural