Mild carbon monoxide exposure impairs the developing auditory system of the rat

Webber, Douglas S.; Korsak, Rose A.; Sininger, Lauren; Sampogna, Sharon; Edmond, John

doi:10.1002/jnr.10809

Cited by 17 publications

(24 citation statements)

References 64 publications

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“…Infants are more susceptible to the toxic effects of CO than adults due to higher metabolic rates and the presence of fetal hemoglobin, which binds CO more avidly than adult hemoglobin [1]. Prenatal CO exposure has been shown to result in decreased birth weight, small infant head circumference, behavioral abnormalities, and disruption in cognitive function while chronic low concentration postnatal CO exposure has been shown to impair the developing rat auditory system [7], [8], [9]. The effects of brief postnatal sub-clinical CO exposure on the developing brain, however, are unknown.…”

Section: Introductionmentioning

confidence: 99%

Neurodevelopmental Consequences of Sub-Clinical Carbon Monoxide Exposure in Newborn Mice

et al. 2012

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Carbon monoxide (CO) exposure at high concentrations results in overt neurotoxicity. Exposure to low CO concentrations occurs commonly yet is usually sub-clinical. Infants are uniquely vulnerable to a variety of toxins, however, the effects of postnatal sub-clinical CO exposure on the developing brain are unknown. Apoptosis occurs normally within the brain during development and is critical for synaptogenesis. Here we demonstrate that brief, postnatal sub-clinical CO exposure inhibits developmental neuroapoptosis resulting in impaired learning, memory, and social behavior. Three hour exposure to 5 ppm or 100 ppm CO impaired cytochrome c release, caspase-3 activation, and apoptosis in neocortex and hippocampus of 10 day old CD-1 mice. CO increased NeuN protein, neuronal numbers, and resulted in megalencephaly. CO-exposed mice demonstrated impaired memory and learning and reduced socialization following exposure. Thus, CO-mediated inhibition of neuroapoptosis might represent an important etiology of acquired neurocognitive impairment and behavioral disorders in children.

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Section: Introductionmentioning

confidence: 99%

Neurodevelopmental Consequences of Sub-Clinical Carbon Monoxide Exposure in Newborn Mice

et al. 2012

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“…Chronic mild postnatal CO exposure has also been shown to impair the developing auditory system (Lopez, 2003; Stockard-Sullivan, 2003; Webber, 2003). Expression of c-Fos, an indicator of neuronal activation following sound stimulation, was found to be significantly decreased in the central nucleus of the inferior colliculus in 27 day old rats following chronic postnatal exposure to between 12 and 50 ppm CO beginning on the eighth day of life (Webber, 2003).…”

Section: Low Concentration Co Exposure and Subclinical Neurotoxicitymentioning

confidence: 99%

“…Expression of c-Fos, an indicator of neuronal activation following sound stimulation, was found to be significantly decreased in the central nucleus of the inferior colliculus in 27 day old rats following chronic postnatal exposure to between 12 and 50 ppm CO beginning on the eighth day of life (Webber, 2003). In addition, chronic postnatal exposure to 50 ppm CO beginning at the onset of myelination was shown to attenuate the amplitude of conduction of the eighth cranial nerve in newborn rats (Stockard-Sullivan, 2003).…”

Section: Low Concentration Co Exposure and Subclinical Neurotoxicitymentioning

confidence: 99%

“…Interestingly, exposure to 100 ppm CO, yielding a mean COHb level of 10.2%, had no effect on eighth cranial nerve conduction suggesting that lower levels of CO exposure were responsible for the pathologic effects (Stockard-Sullivan, 2003). In both of these studies, CO-induced defects persisted into adulthood and failed to recover completely, however, the exact mechanisms remain unknown (Stockard-Sullivan, 2003; Webber, 2003). The authors of these investigations concluded that their results may have implications for auditory neuropathy acquired by children born to tobacco smoking mothers (Stockard-Sullivan, 2003).…”

Section: Low Concentration Co Exposure and Subclinical Neurotoxicitymentioning

confidence: 99%

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Carbon monoxide pollution and neurodevelopment: A public health concern

Levy¹

2015

Neurotoxicology and Teratology

119

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Although an association between air pollution and adverse systemic health effects has been known for years, the effect of pollutants on neurodevelopment has been underappreciated. Recent evidence suggests a possible link between air pollution and neurocognitive impairment and behavioral disorders in children, however, the exact nature of this relationship remains poorly understood. Infants and children are uniquely vulnerable due to the potential for exposure in both the fetal and postnatal environments during critical periods in development. Carbon monoxide (CO), a common component of indoor and outdoor air pollution, can cross the placenta to gain access to the fetal circulation and the developing brain. Thus, CO is of particular interest as a known neurotoxin and a potential public health threat. Here we review overt CO toxicity and the policies regulating CO exposure, detail the evidence suggesting a potential link between CO-associated ambient air pollution, tobacco smoke, and learning and behavioral abnormalities in children, describe the effects of subclinical CO exposure on the brain during development, and provide mechanistic insight into a potential connection between CO exposure and neurodevelopmental outcome. CO can disrupt a number of critical processes in the developing brain, providing a better understanding of how this specific neurotoxin may impair neurodevelopment. However, further investigation is needed to better define the effects of perinatal CO exposure on the immature brain. Current policies regarding CO standards were established based on evidence of cardiovascular risk in adults with pre-existing comorbidities. Thus, recent and emerging data highlighted in this review regarding CO exposure in the fetus and developing child may be important to consider when the standards and guidelines are evaluated and revised in the future.

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“…130–134 Low dose CO exposure in the postnatal period, for example, permanently impaired the developing rodent auditory system and CO-mediated inhibition of natural programmed cell death in the newborn mouse brain resulted in excess number of neurons and long-lasting cognitive and behavioral defects. 134–137 These disruptive effects of CO exposure are likely due to the unique sensitivity and vulnerability of the developing brain to a variety of biologically active agents that can interrupt the critical processes involved in neurodevelopment. 138,139 …”

Section: Biologic Effects Of Comentioning

confidence: 99%

Anesthesia-Related Carbon Monoxide Exposure: Toxicity and Potential Therapy

Levy

2016

Anesthesia &Amp; Analgesia

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Exposure to carbon monoxide (CO) during general anesthesia can result from volatile anesthetic degradation by carbon dioxide absorbents as well as re-breathing of endogenously produced CO. Although adherence to the Anesthesia Patient Safety Foundation guidelines reduces the risk of CO poisoning, patients may still experience a sub-toxic CO exposure during low-flow anesthesia. The consequences of such exposures are relatively unknown. In contrast to the widely recognized toxicity of high CO concentrations, the biological activity of low concentration CO has recently been shown be cytoprotective. As such, low dose CO is being explored as a novel treatment for a variety of different diseases. Here we review the concept of anesthesia-related CO exposure, identify the sources of production, detail the mechanisms of overt CO toxicity, highlight the cellular effects of low dose CO, and discuss the potential therapeutic role for CO as a part of routine anesthetic management.

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Mild carbon monoxide exposure impairs the developing auditory system of the rat

Cited by 17 publications

References 64 publications

Neurodevelopmental Consequences of Sub-Clinical Carbon Monoxide Exposure in Newborn Mice

Neurodevelopmental Consequences of Sub-Clinical Carbon Monoxide Exposure in Newborn Mice

Carbon monoxide pollution and neurodevelopment: A public health concern

Anesthesia-Related Carbon Monoxide Exposure: Toxicity and Potential Therapy

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