The Role of Aquaporin-4 in Cerebral Edema Formation after Focal Cerebral Ischemia in Rats

ABSTRACT

OBJECTIVE: To elucidate the role of aquaporin-4(AQP4) in cerebral edema formation, we studied the expression and subcellular localization of AQP4 in astrocytes after focal cerebral ischemia. METHODS: Cerebral ischemia were induced by permanent middle cerebral artery(MCA) occlusion in rats and estimated by the discoloration after triphenyltetrazolium chloride(TTC) immersion. Change of AQP4 expression were evaluated using western blot. Localization of AQP4 was assessed by confocal microscopy and its interaction with alpha-syntrophin was analyzed by immunoprecipitation. RESULTS: After right MCA occlusion, the size of infarct and number of apoptotic cells increased with time. The ratio of GluR1/GluR2 expression also increased during ischemia. The polarized localization of AQP4 in the endfeet of astrocytes contacting with ventricles, vessels and pia mater was changed into the diffuse distribution in cytoplasm. The interactions of AQP4 and Kir with alpha-syntrophin, an adaptor of dystrophin complex, were disrupted by cerebral ischemia. CONCLUSION: The deranged spatial buffering function of astrocytes due to mislocalized AQP4/Kir4.1 channel as well as increased assembly of Ca2+ permeable AMPA receptors might contribute to the development of edema formation and the excitotoxic neuronal cell death during ischemia.