Monitoring of neurotransmitter amino acids by means of an indwelling cisterna magna catheter: A comparison of two rodent models of fulminant liver failure

Abstract

Alterations of brain and cerebrospinal fluid amino acids have consistently been described in human and experimental fulminant liver failure. To evaluate the significance of such changes in the pathogenesis of hepatic encephalopathy in fulminant liver failure, brain and cerebrospinal fluid amino acids (glutamate, aspartate, GABA, glycine, taurine) were measured at various stages during the development of neurological dysfunction in rats after hepatic devascularization or thioacetamide treatment to induce acute liver failure. To facilitate repetitive removal of cerebrospinal fluid, a technique employing long-term implantation of cisterna magna catheters in conscious, freely moving rats was developed. Brain but not cerebrospinal fluid concentrations of the excitatory amino acids glutamate and aspartate were reduced in both animal models of fulminant liver failure in parallel with deterioration of neurological status. Brain and cerebrospinal fluid GABA levels were not significantly altered. Cerebrospinal fluid glycine levels were increased two to three times in parallel with increasing brain glycine content in the devascularized rat but were unchanged in thioacetamide-induced liver failure, suggesting distinct pathophysiological mechanisms in these two experimental situations. On the other hand, onset of coma in both animal models of fulminant liver failure was accompanied by significantly increased cerebrospinal fluid taurine levels. We suggest that such changes result from taurine release from astrocytes in brain into the extracellular fluid; this is consistent with taurine's role in the regulation of intracellular osmolarity in brain. Sequential measurements of amino acids in the cerebrospinal fluid of small rodents with indwelling cisterna magna catheters adds a useful new approach for exploring the neurobiology of hepatic encephalopathy in fulminant liver failure.