Treatment with BoxA significantly reduced plasma MPO-DNA complexes (144.8% ± 56.2% vs. 275.4% ± 52.5%; Supplemental Figure 12A) and improved ischemic stroke outcomes (53.9 ± 26.7 mm3 vs. 88.2 ± 35.2 mm3; Supplemental Figure 12, B–D), confirming a key role for HMGB1 mediating detrimental NET formation in ischemic stroke. Here, HMGB1 is linked to ischemic stroke.