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Brain expression of the water channels Aquaporin-1 and -4 in mice with acute liver injury, hyperammonemia and brain edema

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Abstract

Cerebral edema is a feared complication to acute liver failure (ALF), but the pathogenesis is still poorly understood. The water channels Aquaporin-1 (Aqp1) and -4 (Aqp4) has been associated with brain edema formation in several neuropathological conditions, indicating a possible role of Aqp1 and/or Aqp4 in ALF mediated brain edema. We induced acute liver injury and hyperammonemia in mice, to evaluate brain edema formation and the parallel expression of Aqp1 and Aqp4 in ALF. Liver injury and hyperammonemia were induced by +D-galactosamine (GLN) plus lipopolysaccharide (LPS) intraperitoneally and intravenous ammonia-acetate (NH4 +), the GLN+LPS+NH4 + group. The vehicle control group (CONTROL) was treated with NaCl and phosphate-buffered saline. The GLN+LPS+NH4 + group showed significantly elevated p-alanine aminotransferase, p-INR and p-ammonium vs. CONTROL (p < 0.001). Cortical brain water content was significantly elevated in the GLN+LPS+NH4 + group vs. CONTROL, mean (SEM) 80.8(0.3) vs 80.0(0.1) % (p < 0.05). Western blot of membrane enriched cortical brain tissue showed significantly upregulation of Aqp4 in the GLN+LPS+NH4 + group vs. CONTROL, mean AU (SEM) 100775(14820) vs. 58857(6266) (p < 0.05), and stationary levels for Aqp1. Aqp1 and Aqp4 mRNA were stationary. This study indicates that Aqp4, but not Aqp1, may be of importance in the pathogenesis of cortical brain edema in mice with ALF.

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Acknowledgments

The Rigshospitalet Research Foundation, University of Copenhagen, Denmark; Savvaerksejer Jeppe Juhl and wife Ovita Juhls Foundation; The Novo Nordisk Foundation; The AP-Møller Foundation; The Brøchner Mortensen Foundation.

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Authors and Affiliations

  1. Department of Hepatology, 2121, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Martin Eefsen, Lars E. Schmidt & Fin S. Larsen

  2. Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark

    Peter Jelnes & Hanne Cathrine Bisgaard

  3. Department of Pathology, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Ben Vainer

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  1. Martin Eefsen
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  2. Peter Jelnes
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  5. Hanne Cathrine Bisgaard
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  6. Fin S. Larsen
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Correspondence to Martin Eefsen.

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Eefsen, M., Jelnes, P., Schmidt, L.E. et al. Brain expression of the water channels Aquaporin-1 and -4 in mice with acute liver injury, hyperammonemia and brain edema. Metab Brain Dis 25, 315–323 (2010). https://doi.org/10.1007/s11011-010-9213-y

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  • DOI: https://doi.org/10.1007/s11011-010-9213-y

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