In this study, we demonstrate that L-4F treatment not only has beneficial effects on BBB integrity (identified by decreased albumin infiltration, increased tight junction protein expression, and AQP-4 expression in astrocyte end-feet), but also on neurovascular remodeling (identified by increased SMC number and enhanced vasodilation), WM remodeling (identified by increased WM density and myelination), and oligodendrogenesis (identified by the increased number of OLs and OPCs) in the ischemic brains in the middle-aged wild-type (ABCAfl/fl) T2DM-stroke mice. The gene discussed is AQP4; the disease is type 2 diabetes mellitus.