UC Irvine

The contribution of neuroinflammatory processes to epilepsy that may follow febrile status epilepticus (FSE) is crucial, as inflammatory mediators offer targets for prevention and intervention strategies. Experimental models suggest that neuroinflammation contributes intrinsically to the generation of fever-related seizures in children. FSE, defined as prolonged febrile seizures (FS), often precedes and likely contributes to a significant subset of adult temporal lobe epilepsy (TLE). Because TLE may be associated with cognitive and emotional problems and is commonly refractory to treatment, unraveling the connections between FSE and TLE and specifically the role of neuroinflammation and related epigenomic mechanisms is of significant translational value. This chapter discusses the contribution of inflammatory mediators to FS and FSE and then focuses on evidence from experimental models for involvement of inflammatory pathways in FSE-related epileptogenesis. Capitalizing on information from both human studies and animal models, we discuss the potential contributions of several salient neuroinflammatory cascades, as well as of blood-brain barrier disruption, microRNAs, and downstream transcriptional regulators, in the context of FSE and epileptogenesis in general. Finally, we highlight the potential efficacy of both pathway-specific blockers and global antiinflammatory strategies for mitigating FSE-related epileptogenesis.