Aquaporin-4 knockdown ameliorates hypoxic-ischemic cerebral edema in newborn piglets.

Emerging evidence indicates that the water channel protein aquaporin 4 (AQP4) plays an essential role in water homeostasis and is implicated in the pathogenesis of brain edema. This study aimed to understand the physiological role of AQP4 in hypoxia-ischemia-mediated cytotoxic brain edema. We specifically knocked down AQP4 expression by intracerebral injection of a plasmid containing AQP4 siRNA into a neonatal piglet model. The success of the hypoxia-ischemia-induced piglet model was confirmed by conventional magnetic resonance imaging and diffusion-weighted imaging. AQP4 knockdown led to reduced brain edema accompanied by a higher apparent diffusion coefficient value, compared to the control group injected with a plasmid containing scrambled siRNA. Real-time polymerase chain reaction and immunohistochemical analysis confirmed that AQP4 siRNA significantly reduced AQP4 mRNA and protein expression. Finally, neurological function analysis revealed that AQP4 knockdown significantly improved neurobehavioral manifestation of the piglets after exposure to hypoxia-ischemia. Taken together, these results indicate that AQP4 plays an important role in mediating brain edema in hypoxic-ischemic encephalopathy. Therefore, AQP4 could be a therapeutic target to ameliorate early-stage brain edema.