AQP4 Knockout Aggravates Ischemia/Reperfusion Injury in Mice

Background and Purpose: The glial water channel aquaporin-4 (AQP4) has been shown to be involved in a wide range of brain disorders. Although its important role in stroke has already been documented, the underlying mechanism was not clarified yet. Therefore, this study was designed to investigate the impacts of AQP4 deletion in ischemia/reperfusion (I/R). Methods and Results: Herein we found a higher mortality and more severe neurological deficits in AQP4 knockout (AQP4-/-) mice after transient middle cerebral artery occlusion while no difference was observed in water content variation during I/R between two genotypes except a higher basal water content developed in AQP4-/- mouse brain, implying the same increment of water content over a higher basal level may provoke an even more elevated intracranial pressure, which might be an important cause of increased mortality in AQP4-/- mice. Moreover, AQP4 knockout aggravated I/R injury with enlarged infarct size and a more serious loss of CA1 neurons accompanied by a striking hypertrophy of astrocytes, suggesting an involvement of AQP4 in astrocytic dysfunction. Conclusions: Our findings provide direct evidence that AQP4 plays a crucial role in the pathogenesis of I/R injury, which may confer a new option for stroke treatment.