Primary cultures of rat astrocytes respond to thiamine deficiency-induced swelling by downregulating aquaporin-4 levels

Imaging studies indicate that cerebral edema is an important consequence of Wernicke's encephalopathy (WE), a disorder caused by thiamine deficiency (TD). We have investigated this problem using a recently developed in vitro astrocyte model of TD. Measurement of cell volume using the 3-O-methylglucose uptake method revealed a dose-dependent swelling of astrocytes during exposure to TD conditions. Time course studies indicated a progressive volume increase up to a maximum of 93% above controls after 4 days of treatment. This swelling then partially resolved, and remained stable for up to 10 days following commencement of TD treatment. Measurement of aquaporin-4 (AQP-4) levels showed a 44% loss after 10 days and a temporal profile consistent with an important role for this water channel protein in astrocyte cell volume changes during TD. Our findings of astrocyte swelling in TD are consistent with previous reports of focal brain edema in cases of WE, and indicate that AQP-4 may be an important target for ameliorating some of the clinical problems associated with this disorder.