Systemic LPS exacerbates ischemic brain damage via an IL-1-dependent pathway. LPS was administered systemically, and the extent of ischemic damage and neurological deficit was assessed 24 h after MCAo. A, LPS significantly increased the volume of ischemic damage. Coadministration of IL-1RA attenuated the effect of LPS. **p < 0.01 versus vehicle (veh); #p < 0.05 versus LPS, one-way ANOVA followed by Student's t test with Bonferroni's correction. Data are presented as mean ± SEM. B, Representative cresyl violet-stained sections illustrate the distribution of ischemic damage after MCAo in vehicle- or LPS-treated mice. C, LPS worsened neurological outcome and coadministration of IL-1RA reduced the number of mice with a severe neurological deficit (score, 3). *p < 0.05 versus vehicle, Kruskal–Wallis test followed by Dunn's multiple-comparison test. Bars show median. n = 6–7 per group.