Microglial activation: an important process in the onset of epilepsy

This study aimed to investigate the effects of microglial activation on the onset of epilepsy. Microglias cultured in vitro were stimulated with different concentrations of coriaria lactone (CL), and the effects on cell cycle and apoptosis were examined using flow cytometry. Then microglia were stimulated with 5×10^-5 mol/L CL, and levels of cyclin D1 and interleukin-1β (IL-1β) mRNA were measured by fluorescence quantitative PCR; tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in supernatant were detected by radioimmunoassay. Finally, microglia-conditioned medium (MCM) obtained after various durations of CL treatment was infused into rat lateral ventricle, and rat behavior was observed and cortical electroencephalograms (EEGs) were recorded. Immunofluorescence staining was used to measure glutamate content in the rat cerebral cortex and hippocampus. Compared with the cell cycle phase distribution in the control group, the percentage of CL-treated cultured microglia in G0/G1 phase was significantly lower, while the percentages of microglia in S phase and G2/M phases were significantly higher. CL increased the gene expression of cyclin D1 and the secretion of TNF-α and IL-1β. Epileptic seizures were induced in rats after intraventricular injection with MCM from CL-treated cells, with animals showing bilateral beard shaking and forelimb tremor. EEGs from these animals exhibited epileptiform waveforms (such as spike waves, sharp waves and spike-slow waves), and glutamate content in the cerebral cortex and hippocampus was significantly increased. CL may therefore activate microglia by promoting proliferation and upregulation of cell factor (e.g., cyclin D1, TNF-α and IL-1β) expression. We have shown that CL-treated MCM can induce the onset of epilepsy in rats in vivo, and its mechanism of action may involve the upregulation of glutamate expression. In summary, microglial activation is an important link in the pathogenesis of the onset of epilepsy.