NOX4 and ischemic stroke: During the acute stage of ischemic stroke, EA or MA could reduce BBB permeability and brain edema by increasing the expression of tight junction proteins ZO-1 and claudin-5 in the ischemic cortex, decreasing the expression of ROS generation, NADPH oxidase 4 (NOX4) and astrocytic aquaporin 4 (AQP4) in the peri-infarct area [100], and inhibiting expression of MMP-2 and MMP-9, AQP4 and APQ9, which are implicated in BBB permeabilization and destruction [101, 102].