This is consistent with previous studies showing that TIMP2 protects against BBB disruption in both ischemic and hemorrhagic stroke.32,33,40,41 TIMP2 is an endogenous inhibitor of matrix metalloproteinase-2 (MMP-2), an MMP that actively regulates ECM turnover/remodeling and BBB integrity in physiological and pathological conditions.41,42 Because MMP-2 is substantially up-regulated in stroke43,44 and increased MMP-2 induces BBB breakdown,32,33,40,41 it is believed that TIMP2 exerts its neuroprotective role in stroke via inhibiting MMP-2. This evidence concerns the gene TIMP2 and hemorrhagic stroke.