(CACL2)-CA-45 AUTORADIOGRAPHY IN BRAIN FROM RABBITS WITH ENCEPHALOPATHY FROM ACUTE LIVER-FAILURE OR ACUTE HYPERAMMONEMIA

In experimental hepatic encephalopathy and hyperammonemia, extracellul ar levels of glutamate are increased in hippocampus and cerebral corte x. It has been suggested that overstimulation of glutamate receptors c auses a pathological entry of calcium into neurons via receptor-operat ed (NMDA- and AMPA-type) or voltage-dependent calcium channels leading to calcium overload and cell death. Neurodegeneration as a result of exposure to excitotoxins, including glutamate, can be localized and qu antified using (CaCl2)-Ca-45 autoradiography. This approach was used t o study cerebral calcium accumulation in rabbits with acute liver fail ure and acute hyperammonemia. Acute liver failure was induced in 6 rab bits, acute hyperammonemia in 4 rabbits; 4 control rabbits received so dium-potassium-acetate. At the start of the experiment 500 mu Ci (CaCl 2)-Ca-45 was given intravenously. After development of severe encephal opathy, the animals were killed by decapitation. All rabbits with acut e liver failure or acute hyperammonemia developed severe encephalopath y, after 13.2+/-1.7 and 19.3+/-0.5 hours respectively (mean+/-SEM). Pl asma ammonia levels were 425+/-46 and 883+/-21 mu mol/l, respectively (p<0.05). Control rabbits maintained normal plasma ammonia levels (13/-5 mu mol/l), demonstrated normal behaviour throughout the study and were sacrificed after 16 hours. Ca-45(2+)-autoradiograms of 40 mu m br ain sections were analyzed semiquantitatively using relative optical d ensity and computerized image analysis. As compared to background leve ls Ca-45 was not increased in hippocampus or any other brain area of r abbits with severe encephalopathy from acute liver failure or acute hy perammonemia. This suggests that, despite increased extracellular brai n glutamate levels in these conditions, glutamate neurotoxicity was no t important for the development of encephalopathy in these rabbits.