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As the immune system is not fully developed at birth, the early years become an important window for infections and for the development of epilepsy. Both central and even peripheral inflammation may impact brain function, promoting opening of the blood\u2013brain\/blood and cerebrospinal barriers and allowing entry of immune cells and cytokines, which in turn may affect neuron function and connections. The resident brain immune cells, microglia, besides providing protection, also affect neurons, myelination, and astrocyte function. They may, via the complement system, remove synapses, both physiologically and pathologically. After seizures during development, activated microglia releases proinflammatory molecules, which are detrimental for neurons, and inhibition of microglial activation shows promising antiepileptogenic effects. In addition to cytokines, seizures and excessive excitability stimulate calpain 2 expression, which can promote neuron loss and contribute to amplification of inflammatory responses via stimulation of proinflammatory cytokines. 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