Fig. 3

Illustration of main targets and sources of pro-ictogenic inflammatory mediators in the brain. The pro-inflammatory molecules can either be produced by brain cells or produced by infiltrating lymphocytes after epileptogenic events. These inflammatory mediators promote the transcription and release of other inflammatory molecules in autocrine and/or paracrine manners, and also induce or aggravate the blood-brain barrier (BBB) dysfunction. Some of them can trigger neuronal over-excitation by disturbing the gliotransmitter metabolism in astrocytes. Besides, they can directly activate their cognate receptors on neurons to induce alterations of expression of glutamate and GABA receptors as well as ion channels. All these pro-inflammatory mediators alter synaptic transmission and promote excitotoxicity, thereby contributing to pathological outcomes. DAMPs: damage-associated molecular pattern molecule; NO: nitric oxide; PAF: platelet-activating factor; PG: prostaglandin; MMP-9: matrix metalloproteinase-9; VEGF: vascular endothelial growth factor; GABA: γ-aminobutyric acid; GM-CSF: granulocyte-macrophage colony-stimulating factor