Modulation of neuroinflammation as a therapeutic strategy for the control of epilepsy

Neuroinflammation plays a pivotal role in the onset and progression of epilepsy. In this review, we critically examine: (1) the dual roles of astrocytes and microglia in maintaining a chronic inflammation and its contribution to epileptogenesis and seizures; (2) the crosstalk between the histamine released by mast cells and the brain histaminergic neurotransmission, an underexplored mechanism for seizures; (3) the potential of inflammatory mediators as biomarkers for predicting prognosis and risk stratification; (4) the shared inflammatory pathways linking epilepsy and Alzheimer's disease, with special attention to reactive astrocyte and ferroptosis markers in identifying individuals at risk; (5) emerging therapeutic strategies, including conventional anti-inflammatory drugs and traditional medicine, for seizure control through modulation of neuroinflammation. With these carefully chosen topics, we introduce new molecular findings reinforcing the crucial role of neuroinflammation in epilepsy and as a marker for epileptogenesis, a topic of special interest for the acquired epilepsies such as hippocampal sclerosis. Moreover, we explored other mechanisms that received far less attention, especially those linking epilepsy with Alzheimer's disease, and the potential role of mast cells in seizures.