The role of the N-methyl-d-aspartate receptor in ketamine-induced apoptosis in rat forebrain culture

Wang, C.; Sadovova, Natalya; Fu, Xin; Schmued, Larry C.; Scallet, Andrew C.; Hanig, Joseph P.; Slikker, William

doi:10.1016/j.neuroscience.2005.01.053

Cited by 176 publications

(145 citation statements)

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“…Activation of NMDARs is essential for long-term potentiation and spatial learning and memory (Malenka and Bear, 2004), and NMDAR blockade results in impaired synaptic plasticity manifested as adverse effects on learning and memory (Sakimura et al, 1995;Shimizu et al, 2000). It has been shown that higher doses of ketamine can induce neuroapoptosis in rodents (Maxwell et al, 2006;Olney et al, 2002a;Wang et al, 2005) and primates (Haberny et al, 2002;Slikker et al, 2007b;Wang et al, 2006) during early development. In agreement, we have previously reported that ketamine induces motor neuron toxicity in zebrafish embryos .…”

Section: Discussionmentioning

confidence: 99%

“…Reports also show that exposure of the developing brain to a clinically relevant cocktail of anesthetics that has both NMDA antagonist and GABA mimetic properties results in an extensive pattern of neuroapoptosis, and subsequent cognitive deficits (Olney et al, 2002b). Several reports have illustrated that ketamine can induce neuronal apoptosis when administered in high doses and/or for prolonged durations during susceptible periods of development in rodents (Maxwell et al, 2006;Olney et al, 2002a;Wang et al, 2005) and primates (Haberny et al, 2002;Slikker et al, 2007a;Wang et al, 2006) and these effects can manifest on later disruptions in cognitive function (Paule et al, 2011). To minimize risks to children exposed to anesthesia, it is paramount to understand how anesthetic drugs affect the developing nervous system and whether those effects can be ameliorated or prevented.…”

Section: Introductionmentioning

confidence: 99%

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Acetyl l-carnitine protects motor neurons and Rohon-Beard sensory neurons against ketamine-induced neurotoxicity in zebrafish embryos

Cuevas

Trickler

Guo

et al. 2013

Neurotoxicology and Teratology

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Ketamine, a non-competitive antagonist of N-methyl-D-aspartate (NMDA) type glutamate receptors is commonly used as a pediatric anesthetic. Multiple studies have shown ketamine to be neurotoxic, particularly when administered during the brain growth spurt. Previously, we have shown that ketamine is detrimental to motor neuron development in the zebrafish embryos. Here, using both wild type (WT) and transgenic (hb9:GFP) zebrafish embryos, we demonstrate that ketamine is neurotoxic to both motor and sensory neurons. Drug absorption studies showed that in the WT embryos, ketamine accumulation was approximately 0.4% of the original dose added to the exposure medium. The transgenic embryos express green fluorescent protein (GFP) localized in the motor neurons making them ideal for evaluating motor neuron development and toxicities in vivo. The hb9:GFP zebrafish embryos (28 h post fertilization) treated with 2 mM ketamine for 20 h demonstrated significant reductions in spinal motor neuron numbers, while co-treatment with acetyl L-carnitine proved to be neuroprotective. In whole mount immunohistochemical studies using WT embryos, a similar effect was observed for the primary sensory neurons. In the ketamine-treated WT embryos, the number of primary sensory Rohon-Beard (RB) neurons was significantly reduced compared to that in controls. However, acetyl L-carnitine co-treatment prevented ketamine-induced adverse effects on the RB neurons. These results suggest that acetyl L-carnitine protects both motor and sensory neurons from ketamine-induced neurotoxicity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Acetyl l-carnitine protects motor neurons and Rohon-Beard sensory neurons against ketamine-induced neurotoxicity in zebrafish embryos

Cuevas

Trickler

Guo

et al. 2013

Neurotoxicology and Teratology

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show abstract

“…For the developing brain, especially in the synapse formation period, the high chloride ion concentration in the cell and the activation of GABA receptor can cause the outflow of chloride ions, depolarization, and the increase of Ca 2+ levels inside the cell, which can cause damage to cells [10].…”

Section: Discussionmentioning

confidence: 99%

“…Students with a history of local anesthesia are predicted to have a score 8.1 points lower than the average (-8.1, 95% CI: -15, -1) and this effect is statistically significant (p = 0.025). Students with a history of general anesthesia are also predicted to have lower scores 10.2) than the average, but the difference is not statistically significant. Conclusions: The present findings suggest that the scores in the College Admission Test may be associated with age, gender, father's education and the use of local anesthetics.…”

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confidence: 89%

Factors that may influence the score in the College Admission Test in China

Ling¹,

Yang²,

Lou³

2017

Arch Med Sci Civil Dis

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A b s t r a c tIntroduction: Many factors may influence the score of the College Admission Test. The purpose of this study was to assess the factors that may predict students' scores in the College Admission Test in China. Material and methods: We sent out 1000 questionnaires which consisted of the following items: objective data on demographic factors, their scores of the test, the year they attended the test, whether they took a set of "art" subjects or a set of "science" subjects, the monthly salary of the whole family, the highest academic degree obtained by the father and mother, the history of past operations and the name and the times of operations undergone, as well as the type of anesthesia received by those who took the College Admission Test. Results: Univariate analyses showed that age, gender, household income, parental education, and anesthesia history may influence College Admission Test scores. These variables were subsequently entered into the multivariate linear regression model. Students with a history of local anesthesia are predicted to have a score 8.1 points lower than the average (-8.1, 95% CI: -15, -1) and this effect is statistically significant (p = 0.025). Students with a history of general anesthesia are also predicted to have lower scores 10.2) than the average, but the difference is not statistically significant. Conclusions: The present findings suggest that the scores in the College Admission Test may be associated with age, gender, father's education and the use of local anesthetics. Ever receiving local anesthesia had a negative impact on College Admission Test scores.

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“…While it is clear that anesthetics cause neuronal cell death in the rodent model when given at significant doses during the brain growth-spurt period [10,30], it is not yet known to what degree similar phenomena also occur in primates. In order to determine if inhaled anestheticinduced neurodegeneration in the developing rat has clinical relevance, nitrous oxide and isoflurane should be examined in a nonhuman primate model that more closely mimics the developing pediatric population [7,31].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Potential Neuronal Toxicity of Inhaled Anesthetics in the Developing Nonhuman Primate

Liu¹,

Zhang²,

Patterson³

et al. 2012

Journal of Drug and Alcohol Research

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Anesthetics have been used for years in pediatric patients without clinical evidence of adverse central nervous system (CNS) sequelae. In the current study, postnatal day (PND) 5-6 rhesus monkeys were exposed to nitrous oxide (N 2 O; 70%) alone, isoflurane (ISO; 1.0%) alone, or N 2 O plus ISO for 8 h. Six hours after completion of anesthetic administration, neuronal toxicity was examined using histochemical and molecular imaging approaches.

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The role of the N-methyl-d-aspartate receptor in ketamine-induced apoptosis in rat forebrain culture

Cited by 176 publications

References 32 publications

Acetyl l-carnitine protects motor neurons and Rohon-Beard sensory neurons against ketamine-induced neurotoxicity in zebrafish embryos

Acetyl l-carnitine protects motor neurons and Rohon-Beard sensory neurons against ketamine-induced neurotoxicity in zebrafish embryos

Factors that may influence the score in the College Admission Test in China

Assessment of Potential Neuronal Toxicity of Inhaled Anesthetics in the Developing Nonhuman Primate

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