Similarly, mechanistic preclinical studies of epilepsy reveal that neuronal activation causes the rapid release of HMGB1 and IL-1β that occur prior to seizure onset resulting in neuronal sensitization to excitation due to alterations in excitatory receptor expression as well as lowered seizure threshold leading to increased seizure frequency and severity with each event (i.e., “kindling”; Maroso et al. 2011). Here, HMGB1 is linked to epilepsy.