Metal Toxicity, Liver Disease and Neurodegeneration
- 6 April 2010
- journal article
- review article
- Published by Springer Nature in Neurotoxicity Research
- Vol. 18 (1) , 100-105
Abstract
Hepatocerebral disorders are serious neuropsychiatric conditions that result from liver failure. These disorders are characterized neuropathologically by varying degrees of neuronal cell death in basal ganglia, cerebellum, and spinal cord, and include clinical entities such as Wilson’s Disease, post-shunt myelopathy, hepatic encephalopathy, and acquired non-Wilsonian hepatocerebral degeneration. Morphologic changes to astrocytes (Alzheimer type II astrocytosis) are a major feature of hepatocerebral disorders. Neurological symptoms include Parkinsonism, cognitive dysfunction, and ataxia. Pathophysiologic mechanisms responsible for cerebral dysfunction and neuronal cell death in hepatocerebral disorders include ammonia toxicity and neurotoxic effects of metals such as copper, manganese, and iron. Molecular mechanisms of neurotoxicity include oxidative/nitrosative stress, glutamate (NMDA)-receptor-mediated excitotoxicity, and neuroinflammatory mechanisms. However, neuronal cell death in hepatocerebral disorders is limited by adaptive mechanisms that may include NMDA-receptor down-regulation, the synthesis of neuroprotective steroids and hypothermia. Management and treatment of hepatocerebral disorders include chelation therapy (Wilson’s Disease), the use of ammonia-lowering agents (lactulose, antibiotics, ornithine aspartate) and liver transplantation.Keywords
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