General Anesthetics in Pediatric Anesthesia: Influences on the Developing Brain

McCann, Mary Ellen; Soriano, Sulpicio G.

doi:10.2174/138945012800675768

Cited by 71 publications

(22 citation statements)

References 92 publications

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“…45 Although evidence continues to support the concept that the developing brain is vulnerable to the adversities associated with general anesthesia, 46 the clinical relevance remains unsettled. 47 …”

Section: Discussionmentioning

confidence: 99%

Retinopathy of prematurity and brain damage in the very preterm newborn

Allred

Capone

Fraioli

et al. 2014

Journal of American Association for Pediatric Ophthalmology and

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Purpose To explain why very preterm newborns who develop retinopathy of prematurity (ROP) appear to be at increased risk of abnormalities of both brain structure and function. Methods A total of 1,085 children born at <28 weeks’ gestation had clinically indicated retinal examinations and had a developmental assessment at 2 years corrected age. Relationships between ROP categories and brain abnormalities were explored using logistic regression models with adjustment for potential confounders. Results The 173 children who had severe ROP, defined as prethreshold ROP (n = 146) or worse (n = 27) were somewhat more likely than their peers without ROP to have brain ultrasound lesions or cerebral palsy. They were approximately twice as likely to have very low Bayley Scales scores. After adjusting for risk factors common to both ROP and brain disorders, infants who developed severe ROP were at increased risk of low Bayley Scales only. Among children with prethreshold ROP, exposure to anesthesia was not associated with low Bayley Scales. Conclusions Some but not all of the association of ROP with brain disorders can be explained by common risk factors. Most of the increased risks of very low Bayley Scales associated with ROP are probably not a consequence of exposure to anesthetic agents.

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Section: Discussionmentioning

confidence: 99%

Retinopathy of prematurity and brain damage in the very preterm newborn

Allred

Capone

Fraioli

et al. 2014

Journal of American Association for Pediatric Ophthalmology and

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show abstract

“…In the developing brain, blocking neuronal activity in general and the NMDA receptor in particular induces neuronal apoptosis (Hetman and Kharebava 2006; Hardingham 2006). This effect has been proposed to underlie long-term neurological deficits in children that were repeatedly exposed to general anesthetics (McCann and Soriano 2012). Hence, HDACis may potentially enhance the risk of neurodevelopmental toxicity of general anesthesia.…”

Section: Discussionmentioning

confidence: 99%

Inhibitors of Histone Deacetylases Enhance Neurotoxicity of DNA Damage

Vashishta

Hetman

2014

Neuromol Med

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The nonselective inhibitors of class I/II histone deacetylases (HDACs) including trichostatin A and the clinically used suberoylanilide hydroxamic acid (SAHA, vorinostat) are neuroprotective in several models of neuronal injury. Here, we report that in cultured cortical neurons from newborn rats and in the cerebral cortex of whole neonate rats, these HDAC inhibitors exacerbated cytotoxicity of the DNA double-strand break (DSB)-inducing anticancer drug etoposide by enhancing apoptosis. Similar neurotoxic interactions were also observed in neurons that were treated with other DNA damaging drugs including cisplatin and camptothecin. In addition, in rat neonates, SAHA increased cortical neuron apoptosis that was induced by a single injection of the NMDA receptor antagonist dizocilpine (MK801). In etoposide-treated neurons, the nonselective HDAC inhibition resulted in more DSBs. It also potentiated etoposide-induced accumulation and phosphorylation of the pro-apoptotic transcription factor p53. Moreover, nonselective HDAC inhibition exacerbated neuronal apoptosis that was induced by the overexpressed p53. Importantly, such effects cannot be fully explained by inhibition of HDAC1, which is known to play a role in DSB repair and regulation of p53. The specific HDAC1 inhibitor MS275 only moderately enhanced etoposide-induced neuronal death. Although in etoposide-treated neurons MS275 increased DSBs, it did not affect activation of p53. Our findings suggest that besides HDAC1, there are other class I/II HDACs that participate in neuronal DNA damage response attenuating neurotoxic consequences of genotoxic insults to the developing brain.

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“…Many of the published reviews on pre-clinical evidence in the field of anaesthetics-induced neurotoxicity in young animals included laboratory findings from prior to the year 2010 [6,7,8,9,10,11]. The aim of this review is to summarise recently available laboratory evidence, especially those being published after 2010, in the field of anaesthetics-induced neurotoxicity and its impact on cognitive function.…”

Section: Introductionmentioning

confidence: 99%

Anaesthetics-Induced Neurotoxicity in Developing Brain: An Update on Preclinical Evidence

Zhou

2014

Brain Sciences

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Every year millions of young people are treated with anaesthetic agents for surgery and sedation in a seemingly safe manner. However, growing and convincing preclinical evidence in rodents and nonhuman primates, together with recent epidemiological observations, suggest that exposure to anaesthetics in common clinical use can be neurotoxic to the developing brain and lead to long-term neurological sequelae. These findings have seriously questioned the safe use of general anaesthetics in obstetric and paediatric patients. The mechanisms and human applicability of anaesthetic neurotoxicity and neuroprotection have remained under intense investigation over the past decade. Ongoing pre-clinical investigation may have significant impact on clinical practice in the near future. This review represents recent developments in this rapidly emerging field. The aim is to summarise recently available laboratory data, especially those being published after 2010, in the field of anaesthetics-induced neurotoxicity and its impact on cognitive function. In addition, we will discuss recent findings in mechanisms of early-life anaesthetics-induced neurotoxicity, the role of human stem cell-derived models in detecting such toxicity, and new potential alleviating strategies.

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General Anesthetics in Pediatric Anesthesia: Influences on the Developing Brain

Cited by 71 publications

References 92 publications

Retinopathy of prematurity and brain damage in the very preterm newborn

Retinopathy of prematurity and brain damage in the very preterm newborn

Inhibitors of Histone Deacetylases Enhance Neurotoxicity of DNA Damage

Anaesthetics-Induced Neurotoxicity in Developing Brain: An Update on Preclinical Evidence

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