Pharmacological blockade of IL-1β/IL-1 receptor type 1 axis during epileptogenesis provides neuroprotection in two rat models of temporal lobe epilepsy.

We studied whether pharmacological blockade of the IL-1β-mediated signaling, rapidly activated in forebrain by epileptogenic injuries, affords neuroprotection in two different rat models of status epilepticus (SE). As secondary outcome, we measured treatment's effect on SE-induced epileptogenesis. IL-1β signaling was blocked by systemic administration of two antiinflammatory drugs, namely human recombinant IL-1 receptor antagonist (anakinra), the naturally occurring and clinically used competitive IL-1 receptor type 1 antagonist, and VX-765 a specific non-peptide inhibitor of IL-1β cleavage and release.

The COX-2 inhibitor parecoxib is neuroprotective but not antiepileptogenic in the pilocarpine model of temporal lobe epilepsy.

The enzyme cyclooxygenase-2 (COX-2), which catalyzes the production of pro-inflammatory prostaglandins, is induced in the brain after various insults, thus contributing to brain inflammatory processes involved in the long-term consequences of such insults. Mounting evidence supports that inflammation may contribute to epileptogenesis and neuronal injury developing after brain insults. Anti-inflammatory treatments, such as selective COX-2 inhibitors, may thus constitute a novel approach for anti-epileptogenesis or disease-modification after brain injuries such as head trauma, cerebral ischemia or status epilepticus (SE).