Injection of anti-HMGB1 monoclonal antibody immediately and 6 h later after cerebral ischemia–reperfusion inhibited the increase of blood–brain barrier permeability, microglia activation, TNFα and iNOS expression, and inhibited MMP9 activity during the acute phase of stroke; conversely, intracerebroventricular injection of HMGB1 aggravated the severity of the infarction [133]. This evidence concerns the gene NOS2 and stroke disorder.