Neurotoxicology and teratology
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Neurotoxicol Teratol · Sep 2011
Inhalation anesthetic-induced neuronal damage in the developing rhesus monkey.
The combination of nitrous oxide gas (N(2)O) and isoflurane (ISO) vapor is commonly used in pediatric surgical procedures for human infants and children to produce unconsciousness and analgesia. Because of obvious limitations it is difficult to thoroughly explore the effects of pediatric anesthetic agents on neurons in human infants or children. Due to the complexity of the primate brain, the monkey is often the animal model of choice for developmental neurotoxicology experiments, and it is in the rhesus monkey that the phenomenon of interest (anesthetic-induced neuronal cell death in the brain) has been previously reported. ⋯ However, neuronal damage was apparent when N(2)O was combined with ISO as indicated by increased numbers of caspase-3-, Silver staining- and Fluoro-Jade C-positive cells in the frontal cortex, temporal gyrus and hippocampus. Electron micrographs indicated typical swelling of the cytoplasm and nuclear condensation in the frontal cortex. These data suggest that prolonged exposure to inhaled anesthetics (a combination of N(2)O and ISO) in the developing rhesus monkey results in neuronal damage, and that the cell death observed is apoptotic and necrotic in nature.
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Neurotoxicol Teratol · Sep 1991
The effect of prenatal cocaine exposure on umbilical cord length in fetal rats.
Umbilical cord length has been considered a reliable indicator of fetal movement. In this study, the effect of prenatal cocaine exposure on umbilical cord length was examined in rats. ⋯ Fetuses exposed to cocaine in utero had significantly shorter umbilical cords than intubated controls, although there were no differences in placental or fetal body weights. These data suggest that prenatal cocaine exposure suppresses fetal movement, which could contribute to some of the long-term effects observed in cocaine-exposed offspring.
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Neurotoxicol Teratol · Nov 2002
Prenatal chlorpyrifos exposure in rats causes persistent behavioral alterations.
Use of chlorpyrifos (CPF) has been curtailed due to its developmental neurotoxicity. In rats, postnatal CPF administration produces lasting changes in cognitive performance, but less information is available about the effects of prenatal exposure. We administered CPF to pregnant rats on gestational days (GD) 17-20, a peak period of neurogenesis, using doses (1 or 5 mg/kg/day) below the threshold for fetal growth impairment. ⋯ Promotional effects of acetylcholine (ACh) on cell differentiation may thus help to offset CPF-induced developmental damage that occurs through other noncholinergic mechanisms. Our results indicate that late prenatal exposure to CPF induces long-term changes in cognitive performance that are distinctly gender-selective. Additional defects may be revealed by similar strategies that subject the animals to acute challenges, thus, uncovering the adaptive mechanisms that maintain basal performance.
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Neurotoxicol Teratol · Jul 1991
Wernicke's encephalopathy and Korsakoff's psychosis: to fortify or not to fortify?
The conventional wisdom suggests that Korsakoff's psychosis, an amnesic disorder associated with prolonged alcohol consumption, is the chronic outcome of a thiamin deficiency first exhibited as Wernicke's encephalopathy. The present paper describes the debate in Australia over whether flour and alcoholic beverages should be fortified with thiamin, in an attempt to prevent Wernicke's encephalopathy and thus Korsakoff's psychosis. We conclude that the scientific evidence linking Wernicke's encephalopathy and Korsakoff's psychosis is tenuous. Certainly, it is not sufficient to support what would amount to mass medication.
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Neurotoxicol Teratol · Mar 2011
Protective effect of L-kynurenine and probenecid on 6-hydroxydopamine-induced striatal toxicity in rats: implications of modulating kynurenate as a protective strategy.
The neuroactive metabolite at the kynunerine pathway, kynurenic acid (KYNA), is a well-known competitive antagonist at the co-agonist glycine site of the N-methyl-D-aspartate receptor (NMDAr), and also decreases the extracellular levels of glutamate by blocking α7-nicotinic acetylcholine receptor (α7-nAchr) located on glutamatergic terminals. KYNA has been often reported to be neuroprotective in different neurotoxic models. The systemic administration of L-kynurenine (L-KYN)--the precursor of KYNA--together with probenecid (PROB)--an inhibitor of organic acids transport--to rodents increases KYNA levels in the brain in a dose-dependent manner. ⋯ For all markers evaluated, we observed protective effects of L-KYN+PROB on the dopaminergic damage induced by 6-OHDA. Our results suggest that this strategy was useful to mitigate dopaminergic toxicity in the hemiparkinsonian model. The combined use of L-KYN and PROB is a valuable tool to modulate glutamatergic and cholinergic activities, presumably by means of increased levels of endogenous KYNA.