Aquaporin-4 in the formation of cerebral edema following severe burns What role do arginine vasopressin levels play?

BACKGROUND: Aquaporin-4 (AQP-4), which is able to rapidly transport water within the brain, is highly expressed in brain tissue. It also plays an important role in the formation of cerebral edema following brain injury. However, the role of AQP-4 in the formation of cerebral edema following severe burns remains unknown. OBJECTIVE: To study changes in AQP-4 protein and mRNA expression during formation of cerebral edema following severe burns, and to explore the correlation between AQP-4 protein and mRNA expression with plasma levels of arginine vasopressin (AVP). DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Research Center of Neuroscience, Chongqing Medical University from 2007 to 2008. MATERIALS: Biotin-labeled goat anti-rabbit antibody was provided by Beijing Zhongshan Biotechnology, China; in situ hybridization kit was provided by Wuhan Boster Biotechnology, China; rabbit anti-AQP-4 polyclonal antibody and horseradish peroxidase-labeled goat anti-rabbit IgG were provided by Chemicon, USA; AVP radioimmunoassay kit was provided by the Research Department of Neurobiology, the Second Military Medical University of Shanghai, China. METHODS: A total of 180 adult, healthy, Wistar rats were randomly assigned to control and burn groups with 30 rats in each group. The burn group was observed at five different time points: 2, 6, 12, 24, and 48 hours after burn. Hair on the mouse back was removed to expose skin on the back. After 1 day, skin with the hair removed was dipped into 100 °C water for 15 seconds to induce grade III burn injury that measures 30% of total burn surface area. MAIN OUTCOME MEASURES: Brain water content was measured using the dry-wet weight method. AQP-4 protein and mRNA expressions were detected using immunohistochemistry, in situ hybridization, Western blot, and reverse transcription-polymerase chain reaction; dynamic changes in plasma AVP were detected using radioimmunoassay. RESULTS: Brain water content gradually increased following severe burn injury. AQP-4 protein and mRNA expressions were upregulated in the supraoptic nucleus, suprachiasmatic nucleus, paraventricular nucleus, hippocampus, choroid plexus, and cerebral cortex. Plasma AVP levels increased following burn injury. AQP-4 protein and mRNA expressions positively correlated with brain water content and AVP levels during formation of cerebral edema (r = 0.870, 0.848, P < 0.01). CONCLUSION: AQP-4 participated in the formation of cerebral edema following burn injury. Plasma AVP upregulated AQP-4 expression in brain tissue, thereby promoting formation of cerebral edema.

BACKGROUND： Aquaporin-4 （AQP-4）, which is able to rapidly transport water within the brain, is highly expressed in brain tissue. It also plays an important role in the formation of cerebral edema following brain injury. However, the role of AQP-4 in the formation of cerebral edema following severe bums remains unknown. OBJECTIVE： To study changes in AQP-4 protein and mRNA expression during formation of cerebral edema following severe burns, and to explore the correlation between AQP-4 protein and mRNA expression with plasma levels of arginine vasopressin （AVP）. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Research Center of Neuroscience, Chongqing Medical University from 2007 to 2008. MATERIALS： Biotin-labeled goat anti-rabbit antibody was provided by Beijing Zhongshan Biotechnology, China; in situ hybridization kit was provided by Wuhan Boster Biotechnology, China; rabbit anti-AQP-4 polyclonal antibody and horseradish peroxidase-labeled goat anti-rabbit IgG were provided by Chemicon, USA; AVP radioimmunoassay kit was provided by the Research Department of Neurobiology, the Second Military Medical University of Shanghai, China. METHODS： A total of 180 adult, healthy, Wistar rats were randomly assigned to control and burn groups with 30 rats in each group. The burn group was observed at five different time points： 2, 6, 12, 24, and 48 hours after burn. Hair on the mouse back was removed to expose skin on the back. After 1 day, skin with the hair removed was dipped into 100℃ water for 15 seconds to induce grade III bum injury that measures 30% of total bum surface area. MAIN OUTCOME MEASURES： Brain water content was measured using the dry-wet weight method. AQP-4 protein and mRNA expressions were detected using immunohistochemistry, in situ hybridization, Western blot, and reverse transcription-polymerase chain reaction; dynamic changes in plasma AVP were detected using radioimmunoassay. RESULTS： Brain water content gradually increased following severe burn injury. AQP-4 protein and mRNA expressions were upregulated in the supraoptic nucleus, suprachiasmatic nucleus, paraventricular nucleus, hippocampus, choroid plexus, and cerebral cortex. Plasma AVP levels increased following burn injury. AQP-4 protein and mRNA expressions positively correlated with brain water content and AVP levels during formation of cerebral edema （r= 0.870, 0.848, P 〈 0.01）. CONCLUSION： AQP-4 participated in the formation of cerebral edema following burn injury. Plasma AVP upregulated AQP-4 expression in brain tissue, thereby promoting formation of cerebral edema.