Brief Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Hepatol. Sep 27, 2013; 5(9): 513-520
Published online Sep 27, 2013. doi: 10.4254/wjh.v5.i9.513
Ciclosporin does not attenuate intracranial hypertension in rats with acute hyperammonaemia
Rikke Hebo Larsen, Mette S Kjær, Martin Eefsen, Fin Stolze Larsen, Peter Nissen Bjerring
Rikke Hebo Larsen, Mette S Kjær, Martin Eefsen, Fin Stolze Larsen, Peter Nissen Bjerring, Department of Hepatology, Rigshospitalet, University Hospital of Copenhagen, 2100 Copenhagen, Denmark
Author contributions: All the authors contributed to this manuscript.
Correspondence to: Peter Nissen Bjerring, PhD, Department of Hepatology, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark. peterbjerring@gmail.com
Telephone: +45-28-976095 Fax: +45-35-452913
Received: April 5, 2013
Revised: June 8, 2013
Accepted: August 20, 2013
Published online: September 27, 2013
Processing time: 179 Days and 13.2 Hours
Abstract

AIM: To investigate the neuroprotective potential of ciclosporin during acute liver failure. We evaluated the effect of intrathecally administered ciclosporin on intracranial pressure, brain water content and aquaporin-4 expression in a rat model with acute hyperammonaemia.

METHODS: Twenty-four male Wistar rats with portacaval anastomosis were randomised into four groups receiving ciclosporin or vehicle and ammonia or saline infusion. Ciclosporin or vehicle was given intrathecally prior to the ammonia or saline infusion. The ammonia or saline infusion was given intravenously for 4 h, while intracranial pressure and arterial pressure was recorded. At the end of the experiment, cerebral cortex and cerebellar brain tissue was analysed for water and aquaporin-4 content.

RESULTS: The following intracranial pressures were found at the end of the experiment: ammonia + ciclosporin: 10.0 ± 1.7 mmHg, ammonia + vehicle: 6.8 ± 1.0 mmHg, saline + ciclosporin: 3.1 ± 0.5 mmHg, saline + vehicle: 3.3 ± 0.6 mmHg. Ammonia infusion had a significant effect on intracranial pressure and brain water content, which both were higher in the groups receiving ammonia (P < 0.001, two-way analysis of variance). Treatment with ciclosporin resulted in relevant tissue concentrations of ciclosporin (> 0.2 micromolar) but did not reduce intracranial pressure after 4 h. Furthermore, ciclosporin did not attenuate the increase in cerebral water content, and did not affect aquaporin-4 expression.

CONCLUSION: Intrathecal administration of ciclosporin does not attenuate intracranial hypertension or brain oedema in rats with portacaval anastomosis and 4 h of ammonia infusion.

Keywords: Brain oedema; Acute liver failure; Neuroprotection; Hyperammonaemia; Ciclosporin

Core tip: Acute liver failure and hyperammonaemia can lead to severe brain oedema. Preserving mitochondrial function by treatment with ciclosporin has shown potential in in vitro studies. In this study we evaluated the effect of ciclosporin in a rat model of acute hyperammonaemia on intracranial pressure, brain water content and expression of the water channel aquaporin-4. We did not find a beneficial effect of ciclosporin on intracranial pressure, brain water content or aquaporin-4 expression.