The possible reasons for the results found in our study are as follows: i) excessive HMGB1 is released owing to brain injury or dysfunction and it leads to elevated HMGB1-TLR4 signaling, which results in increased neuronal excitability; ii) seizure threshold is decreased and easier to reach in the epilepsy cases, thus occurrence of seizure becomes more frequent; iii) proinflammatory cytokines, the release of which is induced by excess HMGB1 and in turn stimulate more release of HMGB1, play key roles in the occurrence and perpetuation of seizures. Here, HMGB1 is linked to epilepsy.