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Prolonged seizures, ischemic, traumatic or infectious insults induce primary and/or secondary opening of the BBB. Through serum proteins (e.g. albumin) and specific signaling cascades (e.g. TGFβ), BBB opening induces the transformation of astroglia into “reactive” or “activated” states which initiates the release of inflammatory cytokines. In addition, vascular injury and BBB opening are associated with neovascularization with the generation of additional leaky vessels. Both the impaired buffering of extracellular potassium (K⁺) and glutamate (glut) and the secreted inflammatory cytokines increase neuronal excitability and network connectivity to yield the epileptic network.