The role of inflammation in etiopathogenesis of pharmacoresistant epilepsy and refractory status epilepticus

Brain inflammation represents a common substrate of pharmacoresistant epilepsy of different etiologies and it can directly affect neuronal excitability. Neuromodulatory properties of some proinflammatory molecules (cytokines, chemokines) may be responsible for hyperexcitability in neuronal networks. The relation between inflammation and epilepsy is reciprocal. The inflammatory processes in the brain may participate in initiating seizure activity and simultaneously they may be a consequence of the recurrence of the seizures. Pharmacological studies on experimental models focused on IL-1 beta/IL-1R1, HMGB1/TLR4 and COX-2/prostaglandin systems demostrate that these inflammatory pathways significantly in triggering and recurring seizure activity. Status epilepticus (SE) leads to development of inflammatory processes which can be detected in brain tissue, cerebrospinal fluid and blood serum. Prolonged seizures and SE lead to fast and prolonged activation of specific inflammatory pathways in brain areas accordant with the epileptogenic zone. Understanding the complex role of inflammation in the generation and exacerbation of epilepsy and development of pharmacoresistance in epilepsy is crucial for the identification of new molecular targets for therapeutic intervention in these patients.