Ciclosporin does not attenuate intracranial hypertension in rats with acute hyperammonaemia.
OBJECTIVE
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.


CONCLUSIONS
Intrathecal administration of ciclosporin does not attenuate intracranial hypertension or brain oedema in rats with portacaval anastomosis and 4 h of ammonia infusion.
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.
Rikke Hebo
RH
Larsen
Mette S
MS
Kjær
Martin
M
Eefsen
Fin Stolze
FS
Larsen
Peter Nissen
PN
Bjerring
Acute liver failure; Brain oedema; Ciclosporin; Hyperammonaemia; Neuroprotection