AGER and Mental deterioration: HMGB1 and RAGE levels were remarkably upregulated after surgery and HMGB1 is supposed to cause cognitive decline via breaking BBB permeability, however, study did not conclude either BBB is disrupted after surgery and relationship between HMGB1 and cognitive decline cannot be ascertained as the study did not selectively block HMGB1 using mAb (He et al., 2012).