Encephalopathies brain neurotoxicity

Pediatric patients are particularly at risk for Al neurotoxicity. The development of the brain occurs in the first year of life. High permeability of the immature blood-brain barrier to Al, the increased uptake of Al via a relatively poorly developed gastrointestinal tract, immature formation and function of the kidneys and high Al to body ratios probably all contribute to the Al toxicity [144, 145, 162-165], Children not on dialysis were intoxicated by Al-containing phosphate binders and developed encephalopathy [78, 162, 164, 166, 167],... 

Because the CNS is sensitive to ammonia, its metabolism in the brain and the neurotoxicity associated with hyperammonia and hepatic encephalopathy (the proximate source of damage in the latter is also ammonia) is reviewed here. Hepatic encephalopathy (HE) or congenital and acquired hyperammonemia result in excessive ammonia accumulation within the CNS. The condition is due... 

With respect to the correlation between liver disorders and the functions of the brain, discussion currently focuses on five hypotheses concerning the development of hepatic encephalopathy (7.) intoxication hypothesis, (2.) neurotransmitter hypothesis, (2.) deficiency hypothesis, (4.) synergistic neurotoxicity, and (J.) hypothesis of primary gliopathy. 

Ciclosporin-induced vasculopathy, with endothelial injury and derangement of the blood-brain barrier, is the postulated mechanism of neurological damage. Transient cerebral perfusion abnormalities, demonstrable in SPECT scans of the brain, have been suggested as a reliable indicator of ciclosporin neurotoxicity (SEDA-20, 344). Clinical symptoms as well as CT and/or MRI scans were very similar to those observed in hypertensive encephalopathy, with predominant and reversible white-matter occipital lesions (23). There was complete neurological recovery in most patients after blood pressure was normalized, and deaths due to intracranial hemorrhage are reported only exceptionally. 

Neurotoxicity can also occur as a result of indirect effects. For example, damage to hepatic, renal, circulatory, or pancreatic structures may result in secondary effects on the function and structure of the nervous system, such as encephalopathy or polyneuropathy. Secondary effects would not cause a substance to be considered neurotoxic, though at high enough doses, neurotoxicity could be evident. Thus, for the purpose of this review, a substance is defined as neurotoxic when it or its metabolites produce adverse effects as a result of direct interactions with the nervous system. It should be noted, nevertheless, that some chemicals may have multiple modes of action and affect the nervous system directly and indirectly. For example, several halogenated compounds (e.g., polychlorinated biphenyls (PCB), polybrominated diphenyl ethers (PBDE)) may interact directly with brain cells, and also affect the development of the nervous system by altering thyroid hormone homeostasis.7 8... 

Gelbard, H. A., James, H. J., Sharer, L. R., Perry, S. W., Saito, Y., Kazee, A. M., Blumberg, B. M., and Epstein, L. G. (1995) Apoptotic neurons in brains from paediatric patients with HIV-1 encephalitis and progressive encephalopathy. Neuropathol. Appl. Neurobiol. 21,208-217. Adle-Biassette, H., Levy, Y., Colombel, M., Poron, F., Natchev, S.,Keohane, C., and Gray, F. (1995) Neuronal apoptosis in HIV infection in adults. Neuropathol. Appl. Neurobiol. 21,218-227. Meucci, 0. and Miller, R. J. (1996) gpl20-induced neurotoxicity in hippocampal pyramidal neuron cultures protective action of TGF-betal. J. Neurosci. 16,4080- 088. 

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