Febrile seizures are the most common type of seizures that 2-14% of infants and preschool children suffering from it in the world. Increasing evidence indicates close relation between inflammatory processes, pathogenesis of seizures and Subsequent Epileptogenesis. Based on associated studies, some of the inflammatory mediators such as prostaglandins, cytokines and complement factors, play a more noted role in promoting inflammation and seizure. These mediators of inflammation apply detrimental effects on learning and memory. It seems plausible that interfering with these molecules or their receptors can affect seizure consequences. We intend to determine the relationship between Toll-like receptor 4 antagonizing in rat pups with febrile seizure and amelioration of memory deficits in adulthood. Materials & Methods: Complex febrile seizure was induced for three Consecutive session during p9-p11 in wistar male rats by a heated chamber. The animals were divided into 7 groups (n=16 for each): Control,that is completely intact, Sham, hyperthermia that received Dimethyl sulfoxide as a solvent. 3rd group was hyperthermia without any injections. In other 3 experimental groups (treatments) different doses of TLR4 receptor antagonist (TAK-242) was injected. 7th group was positive control (pups received the effective dose of antagonist without hyperthermia). Prominent neuroinflammatory factors and receptor (levels of IL-1β, TNF-α and TLR4, respectively) were measured by immunohistochemistry and western blot in rat pup’s hippocampi. Also P11 rats were exposed to video-EEG monitoring and after 50 days adult rat exposed to the Novel Object Recognition Task to test learning and memory. Results: Evaluation of the ictogenic cytokines IL‐1β and TNF-also TLR4 expression post febrile seizure induction proved inflammation progression in the brain of sham and hyperthermic groups. On the other hand, dose-dependent TAK-242 injection significantly ameliorates these factors in treatment groups. NORT showed Adult rats displayed cognitive impairment in sham and patient groups (P <0.05) while the rats performance in treatment with TLR4 antagonist improved (P <0.05 ). Conclusion: It is suggested that this antagonist for TLR4 can exploited as a Preventative barrier for seizure progression and provide a reliable route to improve febrile seizure consequences like memory deficits.

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