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01-09-2010 | Original Paper

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

Authors: Martin Eefsen, Peter Jelnes, Lars E. Schmidt, Ben Vainer, Hanne Cathrine Bisgaard, Fin S. Larsen

Published in: Metabolic Brain Disease | Issue 3/2010

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.

Amiry-Moghaddam M, Xue R, Haug FM, Neely JD, Bhardwaj A, Agre P, Adams ME, Froehner SC, Mori S, Ottersen OP (2004) Alpha-syntrophin deletion removes the perivascular but not endothelial pool of aquaporin-4 at the blood-brain barrier and delays the development of brain edema in an experimental model of acute hyponatremia. FASEB J 18:542–544

Badaut J, Lasbennes F, Magistretti PJ, Regli L (2002) Aquaporins in brain: distribution, physiology, and pathophysiology. J Cereb Blood Flow Metab 22:367–378CrossRefPubMed

Badaut J, Brunet JF, Grollimund L, Hamou MF, Magistretti PJ, Villemure JG, Regli L (2003) Aquaporin 1 and aquaporin 4 expression in human brain after subarachnoid hemorrhage and in peritumoral tissue. Acta Neurochir Suppl 86:495–498PubMed

Bemeur C, Desjardins P, Butterworth RF (2010) Antioxidant and anti-inflammatory effects of mild hypothermia in the attenuation of liver injury due to azoxymethane toxicity in the mouse. Metab Brain Dis 2010 Mar;25(1):23–29

Carmosino M, Procino G, Tamma G, Mannucci R, Svelto M, Valenti G (2007) Trafficking and phosphorylation dynamics of AQP4 in histamine-treated human gastric cells. Biol Cell 99:25–36CrossRefPubMed

Chastre A, Jiang W, Desjardins P, Butterworth RF (2010) Ammonia and proinflammatory cytokines modify expression of genes coding for astrocytic proteins implicated in brain edema in acute liver failure. Metab Brain Dis 2010 Mar;25(1):17–21

Eipel C, Kidess E, Abshagen K, Leminh K, Menger MD, Burkhardt H, Vollmar B (2007) Antileukoproteinase protects against hepatic inflammation, but not apoptosis in the response of D-galactosamine-sensitized mice to lipopolysaccharide. Br J Pharmacol 151:406–413CrossRefPubMed

Ganz R, Swain M, Traber P, DalCanto M, Butterworth RF, Blei AT (1989) Ammonia-induced swelling of rat cerebral cortical slices: implications for the pathogenesis of brain edema in acute hepatic failure. Metab Brain Dis 4:213–223CrossRefPubMed

Hirt L, Ternon B, Price M, Mastour N, Brunet JF, Badaut J (2009) Protective role of early aquaporin 4 induction against postischemic edema formation. J Cereb Blood Flow Metab 29:423–433CrossRefPubMed

Jalan R, Olde Damink SW, Hayes PC, Deutz NE, Lee A (2004) Pathogenesis of intracranial hypertension in acute liver failure: inflammation, ammonia and cerebral blood flow. J Hepatol 41:613–620CrossRefPubMed

Larsen FS, Knudsen GM, Paulson OB, Vilstrup H (1994) Cerebral blood flow autoregulation is absent in rats with thioacetamide-induced hepatic failure. J Hepatol 21:491–495CrossRefPubMed

Madrid R, Le MS, Barrault MB, Janvier K, Benichou S, Merot J (2001) Polarized trafficking and surface expression of the AQP4 water channel are coordinated by serial and regulated interactions with different clathrin-adaptor complexes. EMBO J 20:7008–7021CrossRefPubMed

Manley GT, Fujimura M, Ma T, Noshita N, Filiz F, Bollen AW, Chan P, Verkman AS (2000) Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat Med 6:159–163CrossRefPubMed

Marmarou A, Poll W, Shulman K, Bhagavan H (1978) A simple gravimetric technique for measurement of cerebral edema. J Neurosurg 49:530–537CrossRefPubMed

McCoy E, Sontheimer H (2010) MAPK induces AQP1 expression in astrocytes following injury. Glia 58:209–217CrossRefPubMed

Moe SE, Sorbo JG, Sogaard R, Zeuthen T, Petter OO, Holen T (2008) New isoforms of rat Aquaporin-4. Genomics 91:367–377CrossRefPubMed

Norenberg MD, Baker L, Norenberg LO, Blicharska J, Bruce-Gregorios JH, Neary JT (1991) Ammonia-induced astrocyte swelling in primary culture. Neurochem Res 16:833–836CrossRefPubMed

Oshio K, Binder DK, Liang Y, Bollen A, Feuerstein B, Berger MS, Manley GT (2005) Expression of the aquaporin-1 water channel in human glial tumors. Neurosurgery 56:375–381CrossRefPubMed

Papadopoulos MC, Verkman AS (2005) Aquaporin-4 gene disruption in mice reduces brain swelling and mortality in pneumococcal meningitis. J Biol Chem 280:13906–13912CrossRefPubMed

Rama Rao KV, Chen M, Simard JM, Norenberg MD (2003) Increased aquaporin-4 expression in ammonia-treated cultured astrocytes. NeuroReport 14:2379–2382CrossRefPubMed

Ranjan P, Mishra AM, Kale R, Saraswat VA, Gupta RK (2005) Cytotoxic edema is responsible for raised intracranial pressure in fulminant hepatic failure: in vivo demonstration using diffusion-weighted MRI in human subjects. Metab Brain Dis 20:181–192CrossRefPubMed

Ribeiro MC, Hirt L, Bogousslavsky J, Regli L, Badaut J (2006) Time course of aquaporin expression after transient focal cerebral ischemia in mice. J Neurosci Res 83:1231–1240CrossRef

Swain M, Butterworth RF, Blei AT (1992) Ammonia and related amino acids in the pathogenesis of brain edema in acute ischemic liver failure in rats. Hepatology 15:449–453CrossRefPubMed

Tofteng F, Hauerberg J, Hansen BA, Pedersen CB, Jorgensen L, Larsen FS (2006) Persistent arterial hyperammonemia increases the concentration of glutamine and alanine in the brain and correlates with intracranial pressure in patients with fulminant hepatic failure. J Cereb Blood Flow Metab 26:21–27CrossRefPubMed

Vajda Z, Promeneur D, Doczi T, Sulyok E, Frokiaer J, Ottersen OP, Nielsen S (2000) Increased aquaporin-4 immunoreactivity in rat brain in response to systemic hyponatremia. Biochem Biophys Res Commun 270:495–503CrossRefPubMed

Vajda Z, Pedersen M, Fuchtbauer EM, Wertz K, Stodkilde-Jorgensen H, Sulyok E, Doczi T, Neely JD, Agre P, Frokiaer J, Nielsen S (2002) Delayed onset of brain edema and mislocalization of aquaporin-4 in dystrophin-null transgenic mice. Proc Natl Acad Sci USA 99:13131–13136CrossRefPubMed

Vaquero J, Polson J, Chung C, Helenowski I, Schiodt FV, Reisch J, Lee WM, Blei AT (2003) Infection and the progression of hepatic encephalopathy in acute liver failure. Gastroenterology 125:755–764CrossRefPubMed

Wolburg-Buchholz K, Mack AF, Steiner E, Pfeiffer F, Engelhardt B, Wolburg H (2009) Loss of astrocyte polarity marks blood-brain barrier impairment during experimental autoimmune encephalomyelitis. Acta Neuropathol 118:219–233CrossRefPubMed

Xiao F, Arnold TC, Zhang S, Brown C, Alexander JS, Carden DL, Conrad SA (2004) Cerebral cortical aquaporin-4 expression in brain edema following cardiac arrest in rats. Acad Emerg Med 11:1001–1007CrossRefPubMed

Yang B, Zador Z, Verkman AS (2008) Glial cell aquaporin-4 overexpression in transgenic mice accelerates cytotoxic brain swelling. J Biol Chem 283:15280–15286CrossRefPubMed

Zelenina M, Zelenin S, Bondar AA, Brismar H, Aperia A (2002) Water permeability of aquaporin-4 is decreased by protein kinase C and dopamine. Am J Physiol Renal Physiol 283:F309–F318PubMed

Zhou BR, Gumenscheimer M, Freudenberg M, Galanos C (2003) A striking correlation between lethal activity and apoptotic DNA fragmentation of liver in response of D-galactosamine-sensitized mice to a non-lethal amount of lipopolysaccharide. Acta Pharmacol Sin 24:193–198PubMed

Title: Brain expression of the water channels Aquaporin-1 and -4 in mice with acute liver injury, hyperammonemia and brain edema
Authors: Martin Eefsen
Peter Jelnes
Lars E. Schmidt
Ben Vainer
Hanne Cathrine Bisgaard
Fin S. Larsen
Publication date: 01-09-2010
Publisher: Springer US
Published in: Metabolic Brain Disease / Issue 3/2010
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-010-9213-y

At a glance: The STEP trials

Springer Medicine

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

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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