Neurotoxicology and teratology
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Neurotoxicol Teratol · Mar 2017
ReviewAnesthetic neurotoxicity: Apoptosis and autophagic cell death mediated by calcium dysregulation.
A number of findings suggested that general anesthetics induced neural cell death by apoptosis in various animal models. Although clinical evidence regarding the correlation between anesthetic exposures at young age and subsequent cognitive impairments remains unclear, repeated or consistent exposures to general anesthetics may be a potential harmful risk in developing human brains. The mechanisms underlying the anesthetic neurotoxicity have received extensive attention recently. We will attempt a brief review to summarize current understanding on the role of both apoptosis and autophagic cell death mediated by calcium dysregulation in anesthetic neurotoxicity.
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Neurotoxicol Teratol · Mar 2017
Isoflurane exposure leads to apoptosis of neurons and oligodendrocytes in 20- and 40-day old rhesus macaques.
Previously we reported that a 5-hour exposure of 6-day-old (P6) rhesus macaques to isoflurane triggers robust neuron and oligodendrocyte apoptosis. In an attempt to further describe the window of vulnerability to anesthetic neurotoxicity, we exposed P20 and P40 rhesus macaques to 5h of isoflurane anesthesia or no exposure (control animals). Brains were collected 3h later and examined immunohistochemically to analyze neuronal and glial apoptosis. ⋯ In the isoflurane group, approximately 66% of the apoptotic cells were oligodendrocytes and 34% were neurons. In comparison, in our previous studies on P6 rhesus macaques, approximately 52% of the dying cells were glia and 48% were neurons. In conclusion, the present data suggest that the window of vulnerability for neurons is beginning to close in the P20 and P40 rhesus macaques, but continuing for oligodendrocytes.
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Neurotoxicol Teratol · Mar 2017
ReviewNeuroprotection and neurotoxicity in the developing brain: an update on the effects of dexmedetomidine and xenon.
Growing and consistent preclinical evidence, combined with early clinical epidemiological observations, suggest potentially neurotoxic effects of commonly used anesthetic agents in the developing brain. This has prompted the FDA to issue a safety warning for all sedatives and anesthetics approved for use in children under three years of age. ⋯ Although results from recent clinical trials and case reports have indicated the neuroprotective potential of xenon and dexmedetomidine, additional randomized clinical trials corroborating these studies are necessary. By reviewing both the existing preclinical and clinical evidence on the neuroprotective effects of dexmedetomidine and xenon, we hope to provide insight into the potential clinical efficacy of these agents in the management of pediatric surgical patients.
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Neurotoxicol Teratol · Nov 2015
Visual evoked potential latencies of three-year-old children prenatally exposed to buprenorphine or methadone compared with non-opioid exposed children: The results of a longitudinal study.
This study compared the latency of pattern reversal visual evoked potentials (VEP) of 36-month old children exposed to opioid pharmacotherapy in utero to that of a group of non-exposed children. Pregnant women were enrolled as part of an open-label non-randomised flexible dosing longitudinal study. Participants were 21 children whose mothers were treated with buprenorphine- (n=11) or methadone-pharmacotherapy (n=10) during pregnancy, and 15 children not exposed to opioids in pregnancy. ⋯ Nor were there any significant differences in VEP latencies between children prenatally exposed to methadone and children prenatally exposed to buprenorphine. Head circumference (HC) was significantly associated with P100 latencies for both check sizes. Data from this controlled, non-randomised study suggest that neither buprenorphine nor methadone appear to have any long-term effects on visual maturity assessed at 36months of age.
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Neurotoxicol Teratol · Nov 2015
Embryological exposure to valproic acid induces social interaction deficits in zebrafish (Danio rerio): A developmental behavior analysis.
Changes in social behavior are associated with brain disorders, including mood disorders, stress, schizophrenia, Alzheimer's disease, and autism spectrum disorders (ASD). Autism is a complex neurodevelopmental disorder characterized by deficits in social interaction, impaired communication, anxiety, hyperactivity, and the presence of restricted interests. Zebrafish is one of the most social vertebrates used as a model in biomedical research, contributing to an understanding of the mechanisms that underlie social behavior. ⋯ Furthermore, a social interaction deficit is present at 70dpf and 120dpf. VPA exposure did not affect aggression in the adult stage at 70dpf and 120dpf. This is the first study that demonstrated zebrafish exposed to VPA during the first 48h of development exhibit deficits in social interaction, anxiety, and hyperactivity at different developmental periods.