Effects of mannitol on hypoxic-ischemic brain edema and aquaporin-4 expression in neonatal rats

Brain edema after hypoxic-ischemic brain damage (HIBD) is a serious problem in neonates. Mannitol can mitigate edema; however, the molecular mechanism has not been fully elucidated. It has been reported that aquaporin-4 (AQP4), a member of the water channel protein family, plays a vital role in the development of brain edema. We therefore investigated whether mannitol might alleviate brain edema by regulating the expression of AQP4. In the present study, we used an established neonatal rat model of HIBD. A blood-brain barrier (BBB) permeability test revealed BBB leakage following HIBD, suggesting the vasogenic edema contributed to brain swelling during HIBD. Brain water content analysis indicated that mannitol could relief brain edema induced by HIBD after 6 h. In addition, qPCR showed that mannitol upregulated the expression of AQP4 in the first 48 h following HIBD induction. In conclusion, this study suggests that mannitol could alleviate brain edema after HIBD via upregulating the expression of AQP4. It may provide a novel insight into the treatment of HIBD.