Summary
After a careful characterization, a rat model of fulminant hepatic failure galactosamine-induced was utilized in order to evaluate the neurochemical changes and the histological alterations which occur during the developing of the encephalopathy. Following these studies, normal rats were treated with toxins claimed to be the primary agents of hepatic encephalopathy to recognize those which are able to mimic the behavioral, electrophysiological and neurochemical changes found in the rat model of fulminant hepatic failure. With the limit due to informations coming from an experimental model, the symptoms of HE seem to be attributable to neurotoxic agents such as ammonia. The toxicity of ammonia does not seem to be due to a mere decrease of general brain metabolism, but seems rather to be mediated by an increase, at least in some compartment, of neurotoxic amino acids such as glutamate. Both accumulation of ammonia and the neurotoxic effect of glutamate seem to be potentiated by the described zinc depletion (both in liver and in brain). Hence the final effect of these phenomena is the development of the symptoms of encephalopathy triggered by an imbalance between inibitory and excitatory receptor systems in the brain associated with neuronal alterations which take place early and before the appearance of brain edema.
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Zeneroli, M.L., Baraldi, M. (1990). Neurotransmission in Hepatic Encephalopathy. In: Grisolía, S., Felipo, V., Miñana, MD. (eds) Cirrhosis, Hepatic Encephalopathy, and Ammonium Toxicity. Advances in Experimental Medicine and Biology, vol 272. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5826-8_8
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