Encephalopathy animal models

Pathophysiology of Hepatic Encephalopathy Studies in Animal Models... 

Gammal, S.H., BasUe, A.S., GeUer, D., Skolnick, P., and Jones, E.A. 1990. Reversal of the behavioral and electrophysiological abnormalities of an animal model of hepatic encephalopathy by benzodiazepine receptor Ugands. Hepatology 11 371-378. 

One example of reversible metabohc encephalopathy is that seen in thiamine deficiency. Both animal models and humans with pure thiamine deficiency develop highly specific neurological symptoms. These symptoms can be reversed completely, or dramatically improved, often within hours, by the administration of thiamine. These results are instrumental in leading to the concept of metabolic encephalopathy , a disorder without structural brain changes. From a historical standpoint, there are increasing numbers of such disorders, which are amenable to successful treatment. Sadly, for example, in the case of kemicterus, managed health care has led to an increase in the number of cases due to the early release from hospitals of newborn infants after birth, even before the onset of jaundice. 

The area of metabolic encephalopathies is unique in that animal models of disease closely mimic the symptoms seen in human disorders, allowing excellent correlative studies. Seizures are an example of this feature. Many animal models of experimentally induced seizures are available for study in mice and rats, and the neurochemical alterations before and after anticonvulsive therapy can be carefully studied. These more or less direct comparisons permit a more rapid application of results from animal studies to humans. 

In summary, this book on metabohc encephalopathies is meant to combine and correlate animal and human studies. It is hoped that increased awareness of the importance of early diagnosis and treatment of these disorders may result in a lowering of the incidence of structural changes, and morbidity. These disorders hold a special fascination for both basic scientists and chnical investigators because they are accessible, treatable, and there exist good animal models for study. Therefore, this book pulls together basic and chnical neuroscience issues in the treatment of specific metabolic encephalopathies. 

It was earlier noted that human childhood lead encephalopathy is found with blood lead levels in the range 100-800/tg Pb/100 ml. It is a widely held view that animal models of human lead encephalopathy are of limited value (perhaps due to early experiments on adult animals, which, like man, show relatively little neurological disturbance even with prolonged and intensive dosage). However, this chapter shows that with lead exposure during development, blood levels of the same order of magnitude are associated both in man and rat with comparable encephalopathic lesions. 

Michaelson, I. A., Greenland, R. D. and Roth, W. (1974). Increased brain norepinephrine turnover in lead-exposed rats. Pharmacologist, 16, 250 (abstract 340) Michaelson, I. A. and Sauerhoff, M. W. (1974a). An improved model of lead-induced brain dysfunction in the suckling rat. Toxicol. Appl. Pharmacol., 28, 88 Michaelson, I. A. and Sauerhoff, M. W. (1974b). Animal models of human disease Severe and mild lead encephalopathy in the neonatal rat. Env. Health Perspectives, 7, 201... 

Todd, G.K., and Butterworth, F.R., 2001. In vivo microdialysis in an animal model of neurological disease thiamine deficiency (Wernicke) encephalopathy. Methods. 23 56-61. 

Two developments led neuroscientists as well to reexamine aluminum as a potential neurotoxicant. One was the discovery that aluminum played a role in the encephalopathy associated with kidney dialysis. The other was the implication that it was associated with senile dementia of the Alzheimer type. The connection with dialysis encephalopathy has been established, although a suitable animal model is lacking. The association with Alzheimer s disease is tenuous, but the issue has stimulated a considerable body of work that both illuminates the biological actions of aluminum and provides further knowledge of degenerative processes in the nervous system. The behavioral data in laboratory animals are ambiguous because, to achieve effects, many experimenters have administered the aluminum intracranially, a mode of administration with obvious pitfalls. A useful summary of the recent literature appears in the volume edited by Liss. ... 

Michaelson, I. A., and Sauerhoff, M. W. (1974). Animal models of human disease Severe and mild encephalopathy in the neonatal rat. Environ. Hlth. Persp. 7, 201-225. 

Bornschein, R., Pearson, D. and Reiter, L. (1980) Behavioral effects of moderate lead exposure in children and animal models Part 2, animal studies. CRC Cril Rev. Toxicol, 7, 101-152 Bradley, J.E. and Baumgartner, R.J. (1958) Subsequent mental development of children with lead encephalopathy as related to type of treatment. ]. Ped., 53, 311-315 Cory-Slechta, D.A. (1984) The behavioral toxicity of lead problems and perspectives, in Thompson, T., Dews, P.B. and Barrett, J.E. (eds.). Advances in Behavioral Pharmacology, Vol. 4 (New York Academic Press), pp. 211-255... 

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