Figure 2. Blood HMGB1 levels increase before epilepsy onset in electrical SE–exposed rats and predict therapeutic response to antiinflammatory drugs.

Longitudinal analysis of total HMGB1 and levels of acetylated, reduced, and disulfide isoforms in blood plasma at representative time points of disease development in SE-exposed rats receiving treatment (drug) or corresponding vehicle (see key). Treatment included anakinra+BoxA+ifenprodil (SE+drug) (detailed protocol in Methods; Supplemental Figure 5A). Data are shown as mean ± SEM (n = 9 rats each group; dot plots are shown in Supplemental Figure 7). Rats are the same as reported in Figure 3. *P < 0.05; **P < 0.01, 1-way ANOVA (referred to both isoforms in each bar, except for prodromal phase, where P < 0.01 in SE+drug versus SE+vehicle refers only to reduced HMGB1). The acetylated isoform level in the chronic epilepsy phase (SE+vehicle) was significantly different from corresponding levels at disease onset and prodromal phases (P < 0.01, repeated measures 1-way ANOVA). The disulfide isoform (SE+vehicle) level at disease onset and in the chronic epilepsy phase was significantly different from the corresponding level in the prodromal phase (P < 0.05 and P < 0.01, respectively); the disulfide isoform level in the chronic phase was significantly different from the corresponding level at disease onset (P < 0.05, repeated measures 1-way ANOVA).