DECREASED GLUTAMATE TRANSPORTER (GLT-1) EXPRESSION IN FRONTAL-CORTEX OF RATS WITH ACUTE LIVER-FAILURE

It has been suggested that reduced astrocytic uptake of neuronally rel eased glutamate contributes to the pathogenesis of hepatic encephalopa thy in acute liver failure. In order to further address this issue, th e recently cloned and sequenced astrocytic glutamate transporter GLT-1 was studied in brain preparations from rats with ischemic liver failu re induced by portacaval anastomosis followed 24 h later by hepatic ar tery ligation and from appropriate sham-operated controls. GLT-1 expre ssion was studied using reverse transcriptase-polymerase chain reactio n (RT-PCR). Expression of GLT-1 transcript was significantly decreased in frontal cortex at coma stages of acute liver failure. Western blot ting using a polyclonal antibody to GLT-1 revealed a concomitant decre ase in expression of transporter protein in the brains of rats with ac ute liver failure. Reduced capacity of astrocytes to reuptake neuronal ly released glutamate, resulting from a GLT-1 transporter deficit and the consequently compromised neuron-astrocytic trafficking of glutamat e could contribute to the pathogenesis of hepatic encephalopathy and b rain edema, two major complications of acute liver failure. (C) 1997 E lsevier Science Ireland Ltd.