Finding a better drug for epilepsy: Antiinflammatory targets

Abstract

This monograph summarizes one of the sessions of the XI Workshop on Neurobiology of Epilepsy (WONOEP), and provides a critical review of the current state of the field. Speakers and discussants focused on several broad topics: (1) The co-existence of inflammatory processes encompassing several distinct signal-transduction pathways with the epileptogenic process; (2) evidence for the contribution of specific inflammatory molecules and processes to the onset and progression of epilepsy, as well as to epilepsy-related morbidities including depression; (3) the complexity and intricate cross-talk of the pathways involved in inflammation, and the discrete, often opposite roles of a given mediator in neurons vs other cell types. These complexities highlight the challenges confronting the field as it aims to define inflammatory molecules as promising targets for epilepsy prevention and treatment.

Origins of Temporal Lobe Epilepsy: Febrile Seizures and Febrile Status Epilepticus

“…While compelling, blocking IL-1β production and signaling in other models of epileptogenesis (electrical SE and pilocarpine) did not change spontaneous seizure onset, intensity or duration [97]. While these results would need to be replicated in the more naturalistic FSE model to enable inferences about translation to FSE related TLE, they suggest that pan-inflammatory interventions rather than targeting individual cytokines might be tried [78].…”

“…These models allow for causal and mechanistic studies to be carried out and the time frame of prospective studies investigating the evolution of FSE to TLE is shortened [52,78]. However, creating such a model is hampered by the fact that immature rodents do not readily develop fever [28,52].…”

Successful surgical treatment of an inflammatory lesion associated with new-onset refractory status epilepticus

“…The results with wide-spectrum immunomodulatory treatment regimens have been disappointing; therefore, exploration of new antiinflammatory strategies is warranted. 7,20 Molecular imaging with AMT, or other imaging approaches targeting molecular mechanisms associated with neuroinflammation, 13 can offer a noninvasive way to assess presence, severity, and extent of seizure-associated inflammatory changes in the epileptic brain. These modalities could be instrumental not only when surgery is being considered but also in clinical trials as biomarkers when testing novel antiinflammatory approaches.…”

Alpha melanocyte stimulating hormone (α-MSH) does not modify pentylenetetrazol- and pilocarpine-induced seizures

“…Neurotrauma, stroke, infection, and febrile seizures are all associated with acute seizures and increased risk of developing epilepsy (Dedeurwaerdere et al, 2012). Several lines of evidence support a relationship between inflammation and epilepsy (Cremer et al, 2009;Dedeurwaerdere et al, 2012;Perucca et al, 2007;Vezzani et al, 2011a).…”

“…Several lines of evidence support a relationship between inflammation and epilepsy (Cremer et al, 2009;Dedeurwaerdere et al, 2012;Perucca et al, 2007;Vezzani et al, 2011a). Inflammation is triggered by molecular patterns associated to pathogens (PAMPs) or molecular patterns associated to damage (DAMPS) .…”