In contrast, accumulating evidence also shows that activation of the JAK2/STAT3 signaling pathway can increase the expression of the high mobility group box 1 protein or HMGB1, leading to aggravation of post-ischemic inflammatory responses [67–69] and that reducing STAT3 activation improves functional performance and decreased neuronal damage after stroke [16, 65]. This evidence concerns the gene HMGB1 and stroke disorder.