Effects of halothane on the development of rat brain: A Golgi study of dendritic growth

Uemura, Etsuro; Ireland, William P.; Levin, Edward D.; Bowman, Robert E.

doi:10.1016/0014-4886(85)90002-0

Cited by 39 publications

(13 citation statements)

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“…The relative homogeneity of anesthetic technique is an experimental advantage, but conversely we cannot comment of the potential of anesthetics other than halothane26,40 and nitrous oxide 2,7 to cause neurodegeneration. Insufficient numbers of children received ketamine to perform a separate analysis for this drug.…”

Section: Discussionmentioning

confidence: 92%

“…Exposure of immature animals to compounds with gamma-aminobutyric acid-mimetic receptor-agonist or N-methyl d-aspartate receptor-antagonist properties induces apoptotic degeneration of neurons in various brain regions 1–4,7,23. In particular, several drugs with sedative and anesthetic properties (including isoflurane, nitrous oxide, ketamine, benzodiazepines, halothane, and propofol) produce neurodegeneration when administered at sufficient doses and durations of exposure 7,8,23–26. In some animal models, these histological changes have been associated with impaired learning and memory assessed by water and radial arm mazes 7,27…”

Section: Discussionmentioning

confidence: 99%

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Early Exposure to Anesthesia and Learning Disabilities in a Population-based Birth Cohort

et al. 2009

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Background Anesthetic drugs administered to immature animals may cause neurohistopathologic changes and alterations in behavior. We studied association between anesthetic exposure prior to age 4 and the development of reading, written language and math learning disabilities (LD). Methods This was a population-based, retrospective birth cohort study. The educational and medical records of all children born to mothers residing in five townships of Olmsted County, Minnesota from 1976–1982 and who remained in the community at 5 years of age were reviewed to identify children with LD. Cox proportional hazards regression was used to calculate hazard ratios for anesthetic exposure as a predictor of LD, adjusting for gestational age at birth, gender, and birth weight. Results Of the 5,357 children in this cohort, 593 received general anesthesia before age 4. Compared to those not receiving anesthesia (N=4,764), a single exposure to anesthesia (N=449) was not associated with an increased risk of LD (hazard ratio =1.0, 95% CI 0.79–1.27). However, children receiving 2 anesthetics (N=100) or ≥3 anesthetics (N=44) were at increased risk for LD (hazard ratio =1.59, 95% CI 1.06–2.37, and hazard ratio =2.60, 95% CI 1.60–4.24, respectively). The risk for LD increased with longer cumulative duration of anesthesia exposure (expressed as a continuous variable) (P=0.016). Conclusion Exposure to anesthesia was a significant risk factor for the later development of LD in children receiving multiple, but not single anesthetics. We cannot determine whether anesthesia itself may contribute to LD, or whether the need for anesthesia is a marker for other unidentified factors that contribute to LD.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Early Exposure to Anesthesia and Learning Disabilities in a Population-based Birth Cohort

et al. 2009

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“…These concerns were first raised in the 1970s and 1980s by studies in which long-term, chronic exposure to low levels of halothane from gestation through the early postnatal period in rodents resulted in poorer performance in behavioral testing as well as disturbances in synaptogenesis and neurite development. 1–3 The clinical question driving this work was a concern that chronic exposure to anesthetic gases in the operating room might pose a risk to operating room personnel who are pregnant. More recently the focus of investigation has been on whether a single GA exposure or several discrete exposures at clinically relevant doses can impair brain development.…”

Section: Introductionmentioning

confidence: 99%

Anesthetics Interfere With the Polarization of Developing Cortical Neurons

Mintz

Smith

Barrett

et al. 2012

Journal of Neurosurgical Anesthesiology

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Numerous studies from the clinical and preclinical literature indicate that general anesthetic agents have toxic effects on the developing brain, but the mechanism of this toxicity is still unknown. Previous studies have focused on the effects of anesthetics on cell survival, dendrite elaboration, and synapse formation, but little attention has been paid to possible effects of anesthetics on the developing axon. Using dissociated mouse cortical neurons in culture, we found that isoflurane delays the acquisition of neuronal polarity by interfering with axon specification. The magnitude of this effect is dependent on isoflurane concentration and exposure time over clinically relevant ranges, and it is neither a precursor to nor the result of neuronal cell death. Propofol also appears to interfere with the acquisition of neuronal polarity, but the mechanism does not require activity at GABAA receptors. Rather, the delay in axon specification likely results from a slowing of the extension of pre-polarized neurites. The effect is not unique to isoflurane as propofol also appears to interfere with the acquisition of neuronal polarity. These findings demonstrate that anesthetics may interfere with brain development via effects on axon growth and specification, thus introducing a new potential target in the search for mechanisms of pediatric anesthetic neurotoxicity.

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“…The neurotoxic effects of general anesthetics (GAs) have been widely concerned ever since the report of halothane-related morphologic changes and functional deficits of the brain in rats (Uemura et al, 1985) and the striking finding of anesthetics mediated apoptosis in developing brains (Jevtovic-Todorovic et al, 2003). Accumulating evidence suggested that many anesthetics including midazolam (Young et al, 2005), ketamine (Fredriksson et al, 2004; Garcia et al, 2003; Hayashi et al, 2002; Slikker et al, 2007; Young et al, 2005; Zou et al, 2009a; Zou et al, 2009b), propofol (Cattano et al, 2008; Pesic et al, 2009; Vutskits et al, 2005), isoflurane (Istaphanous et al, 2011; Loepke et al, 2009; Ma et al, 2007; Nikizad et al, 2007; Palanisamy et al, 2011; Sanders et al, 2009), sevoflurane (Istaphanous et al, 2011; Satomoto et al, 2009; Zhang et al, 2008), and desflurane (Istaphanous et al, 2011), induced neural cell death by apoptosis in various tissue cultures and animal models.…”

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confidence: 99%

Anesthetic neurotoxicity: Apoptosis and autophagic cell death mediated by calcium dysregulation

Yang

Wei

2017

Neurotoxicology and Teratology

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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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Effects of halothane on the development of rat brain: A Golgi study of dendritic growth

Cited by 39 publications

References 38 publications

Early Exposure to Anesthesia and Learning Disabilities in a Population-based Birth Cohort

Early Exposure to Anesthesia and Learning Disabilities in a Population-based Birth Cohort

Anesthetics Interfere With the Polarization of Developing Cortical Neurons

Anesthetic neurotoxicity: Apoptosis and autophagic cell death mediated by calcium dysregulation

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