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, microglia 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.

中文翻译：

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小胶质细胞耗竭加剧小鼠急性和慢性癫痫发作的严重程度


小胶质细胞是中枢神经系统的常驻免疫细胞，参与多种神经系统疾病。在这里，我们使用小胶质细胞消融方法确定了小胶质细胞在癫痫发生中的功能。使用三种不同的小胶质细胞特异性遗传工具：CX3CR1CreER/+:R26iDTA/+、CX3CR1CreER/+:R26iDTR/+ 和 CX3CR1CreER/+:Csf1rFlox/Flox 小鼠。我们发现小胶质细胞耗竭导致红藻氨酸（KA）诱导的癫痫持续状态更严重、死亡率更高以及海马神经元变性增加。在 KA 诱导的慢性自发性复发性癫痫发作中，小胶质细胞耗竭增加了癫痫发作频率、发作间期峰值和癫痫发作持续时间。因此，小胶质细胞耗竭会加重 KA 诱发的急性和慢性癫痫发作的严重程度。有趣的是，小胶质细胞的重新增殖逆转了 KA 诱导的癫痫持续状态的消耗效应。我们的结果证明小胶质细胞在抑制急性和慢性癫痫发作方面具有有益作用，这表明小胶质细胞是治疗癫痫的潜在治疗靶点。