HMGB1 and ischemia: As anti-HMGB1 mAb therapy has been shown to suppress most of the events relevant to brain inflammatory responses after ischemia and hemorrhage—i.e., induction of cytokines, glia activation, and facilitation of immune cell migration [15,16]—it may be possible that the HMGB1 released from neurons and other brain cells functions farther upstream than the other components in the inflammation cascade after insult, leading to a disruption of BBB integrity [26,63] (Figure 4).