Under ischemic challenges, NKCC1- and AQP4-mediated astrocytic swelling leads to glutamate-mediated excitotoxicity, excessive nitric oxide (NO) production, and cytokine [such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α] release, which subsequently promote BBB disruption in the ischemic area, resulting in exacerbation of cerebral edema [11, 12]. Here, AQP4 is linked to brain edema.