Moreover, experimental epilepsy models demonstrated that blockade of either HMGB1 or genetic deletion of TLR4 using neutralizing antibodies significantly reduced seizure incidence, thereby validating the pathogenic role of the HMGB1/TLR4 pathway in epilepsy (Zwilling et al., 1995; Schoenmakers and Van de Ven, 1997; Xiao et al., 2011; Ramstein et al., 1999). This evidence concerns the gene TLR4 and epilepsy.