Loss of noradrenaline transporter sites in frontal cortex of rats with acute (ischemic) liver failure

There is increasing evidence that central noradrenaline (NA) transport mech anisms are implicated in the central nervous system complications of acute liver failure. In order to assess this possibility, binding sites for the h igh affinity NA transporter ligand [H-3]-nisoxetine were measured by quanti tative receptor autoradiography in the brains of rats with acute liver fail ure resulting from hepatic devascularization and in appropriate controls. I n vivo microdialysis was used to measure extracellular brain concentrations of NA. Severe encephalopathy resulted in a significant loss of [3H]-nisoxe tine sites in frontal cortex and a concomitant increase in extracellular br ain concentrations of NA in rats with acute liver failure. A loss of transp orter sites was also observed in thalamus of rats with acute liver failure. This loss of NA transporter sites could result from depletion of central N A stores due to a reserpine-like effect of ammonia which is known to accumu late to millimolar concentrations in brain in ischemic liver failure. Impai red NA transport and the consequent increase in synaptic concentrations and increased stimulation of neuronal and astrocytic noradrenergic receptors c ould be implicated in the pathogenesis of the encephalopathy and brain edem a characteristic of acute liver failure. (C) 2000 Elsevier Science Ltd. All rights reserved.