Review articleChemokines as new inflammatory players in the pathogenesis of epilepsy

- Chemokines signaling exerts multiple actions in the brain in both physiological and pathological conditions.
- CCL2, CCL3, CCL5 and CX3CL1 have a key role in epilepsy.
- CCL2, CCL3, CCL5, CX3CL1 and their receptors may represent new therapeutic targets for seizure control.

A large series of clinical and experimental studies supports a link between inflammation and epilepsy, indicating that inflammatory processes within the brain are important contributors to seizure recurrence and precipitation. Systemic inflammation can precipitate seizures in children suffering from epileptic encephalopathies, and hallmarks of a chronic inflammatory state have been found in patients with temporal lobe epilepsy. Research performed on animal models of epilepsy further corroborates the idea that seizures upregulate inflammatory mediators, which in turn may enhance brain excitability and neuronal degeneration. Several inflammatory molecules and their signaling pathways have been implicated in epilepsy. Among these, the chemokine pathway has increasingly gained attention. Chemokines are small cytokines secreted by blood cells, which act as chemoattractants for leukocyte migration. Recent studies indicate that chemokines and their receptors are also produced by brain cells, and are involved in various neurological disorders including epilepsy. In this review, we will focus on a subset of pro-inflammatory chemokines (namely CCL2, CCL3, CCL5, CX3CL1) and their receptors, and their increasingly recognized role in seizure control.