The neuroprotection of Ex-4 was also regarded as a potential therapeutic target in neurodegenerative disease [32] and our data further confirmed PEx-4 was more efficient in reducing ischemic brain-induced edema and injury, which may be related to aquaporin-4-mediated water uptake and compression of the adjacent capillary lumen [33]. Here, AQP4 is linked to neurodegenerative disease.