Neuroprotective and antiepileptogenic effects of combination of anti-inflammatory drugs in the immature brain

Background: inflammatory signaling elicited by prolonged seizures can be contributory to neuronal injury as well as adverse plasticity leading to the development of spontaneous recurrent seizures (epilepsy) and associated co-morbidities. in this study,developing rat pups were subjected to lithium-pilocarpine status epilepticus (se) at 2 and 3 weeks of age to study the effect of anti-inflammatory drugs (aid) on se-induced hippocampal injury and the development of spontaneous seizures. findings: we selected aids directed against interleukin-1 receptors (il-1ra),a cyclooxygenase-2 (cox-2) inhibitor (cay 10404),and an antagonist of microglia activation of caspase-1 (minocycline). acute injury after se was studied in the 2-week-old rats 24 h after se. development of recurrent spontaneous seizures was studied in 3-week-old rats subjected to se 4 months after the initial insult.none of those aids were effective in attenuating ca1 injury in the 2-week-old pups or in limiting the development of spontaneous seizures in 3-week-old pups when administered individually. when empiric binary combinations of these drugs were tried,the combined targeting of il-1r and cox-2 resulted in attenuation of acute ca1 injury,as determined 24 h after se,in those animals. the same combination administered for 10 days following se in 3-week-old rats,reduced the development of spontaneous recurrent seizures and limited the extent of mossy fiber sprouting. conclusions: deployment of an empirically designed 'drug cocktail' targeting multiple inflammatory signaling pathways for a limited duration after an initial insult like se may provide a practical approach to neuroprotection and anti-epileptogenic therapy. © 2013 kwon et al; licensee biomed central ltd.