GLUTAMINE-METABOLISM AND NEUROPATHOLOGIC DISORDERS IN EXPERIMENTAL HEPATIC-ENCEPHALOPATHY - EFFECT OF TRANSPLANTED HEPATOCYTES

Background. Physiopathology of hepatic encephalopathy remains unclear. Recent studies have suggested that ammonia would not act by itself bu t through an increase in glutamine in the brain. We have previously de monstrated that transplantation of syngeneic into the spleen was able to correct both behavioral deficits and plasma amino acid changes obse rved in portacaval shunted rats. The aim of the present work was to sh ow a correlation between the correction of chronic hepatic encephalopa thy by means of intrastructural aspects of astrocytes. Methods. Inbred male Wistar Furth rats were divided into three groups: sham-operated rats (n = 10), rats subjected to portacaval shunt (n = 10), and rats s ubjected to portacaval shunt and intrasplenic hepatocellular transplan tation of 10(7) hepatocytes isolated from livers of syngeneic rats (n = 10). Chronic hepatic encephalopathy was quantified 30 and 60 days af ter operation by means of nose-poke exploration and spontaneous activi ty. Pathologic examination and measurement of glutamine concentrations in the corpus striatus and in the cerebral cortex were performed 60 d ays after operation. Results. Portacaval shunt rats showed reduced spo ntaneous activity and nose-poke exploration scores. After portacaval s hunt a significant glutamine increase occurred in the corpus striatus and in the cerebral cortex when compared with sham rats (p < 0.05). Ul trastructural examination showed modification of astrocytes named Alzh eimer type II after portacaval shunt. Correction of behavioral abnorma lities by means of intrasplenic hepatocyte transplantation was associa ted with partial correction of striatal glutamine increase and with de crease in astrocyte alterations. Cortex glutamine concentration in por tacaval shunt-intrasplenic hepatocyte transplantation group and in por tacaval shunt rats did not differ significantly. Conclusions. These da ta show that intrasplenic hepatocyte transplantation not only prevents neurologic disorders of hepatic encephalopathy but can also decrease glutamine and ultrastructural alterations in the corpus striatus in an experimental model of chronic liver failure. These data are in favor of the involvement of glutamine in chronic hepatic encephalopathy. The se results suggest that intrasplenic hepatocyte transplantation might be of therapeutic interest in chronic liver failure.