Lipopolysaccharide (LPS) increases susceptibility to epilepsy via interleukin-1 type 1 receptor signaling.

Epilepsy is the most common disease of the nervous system, characterized by aberrant normal brain activity. Neuroinflammation is a prominent feature in the brain in epileptic humans and animal models of epilepsy. However, it remains elusive as to how peripheral inflammation affects epilepsy. Herein we demonstrated significantly greater seizure susceptibility and severity of epilepsy under kainic acid (KA) via intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) in mouse model of epilepsy. Nissl staining was employed for assessment of the neuronal damage, immunofluorescence for staining of the microglial cells and astrocytes in the mouse brain slices, and ELISA for detection of the changes of inflammatory factors. We observed a smaller population of viable neurons in CA1 and CA3 regions, a greater population of IBA-1-positive and GFAP-positive cells, with a significant upregulation of IL-1β and IL-6 in hippocampus of epileptic mice when treated with LPS, indicating that LPS aggravates hippocampal neuron injury in epilepsy, and induces neuroinflammation in the hippocampus. In addition, we provide an evident increase in BrdU/DCX and Nestin cell populations in dentate gyrus (DG) in LPS-treated group, versus saline group on epileptic mouse model, which demonstrated LPS treatment enhanced hippocampal neurogenesis. In order to investigate whether interleukin-1 type 1 (IL-1R1) signaling is involved in this process, we adopted IL-1R1 globally restored mice (IL-1R1) as an IL-1R1 reporter to visualize labeling of IL-1R1 mRNA and protein by means of RFP staining. Strikingly, the RFP immunofluorescence revealed increased IL-1R1 expression in LPS-treated group, versus saline group. Further, blockage of central IL-1R1 alleviated seizure susceptibility and severity of epilepsy. In summary, our findings suggested that LPS could enhance central inflammatory response and aggravate the susceptibility to epileptic seizure, which we postulated to be mediated by IL-1R1.