The impact of early exposure to general anesthesia on visual and neurocognitive development

Wong-Kee-You, Audrey; Loveridge-Easther, Cam; Mueller, Claudia; Simon, Noah; Good, William V.

doi:10.1016/j.survophthal.2022.08.006

Cited by 5 publications

(5 citation statements)

References 146 publications

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“…While PND occurred frequently following surgery and anesthesia, determining whether PND results from anesthesia, surgery, or a combination of both remains a challenge to date 2–5 . The impact of general anesthesia on neurodevelopment or neurotoxicity was controversial in human studies 6,7 . But in animal experiments, sevoflurane and isoflurane, two commonly used inhalational anesthetics in general anesthesia, were verified and extensively studied regarding their effect on vulnerable brain such as neonatal or aging brain 8,9 …”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4][5] The impact of general anesthesia on neurodevelopment or neurotoxicity was controversial in human studies. 6,7 But in animal experiments, sevoflurane and isoflurane, two commonly used inhalational anesthetics in general anesthesia, were verified and extensively studied regarding their effect on vulnerable brain such as neonatal or aging brain. 8,9 Iron, as an essential metal element of every living organism, was involved into many biological processes such as energy metabolism, DNA synthesis, repair, and regulation of signaling pathway.…”

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confidence: 99%

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Dysregulation of iron homeostasis and ferroptosis in sevoflurane and isoflurane associated perioperative neurocognitive disorders

Miao,

Han,

Wang

et al. 2024

CNS Neurosci Ther

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In recent years, sevoflurane and isoflurane are the most popular anesthetics in general anesthesia for their safe, rapid onset, and well tolerant. Nevertheless, many studies reported their neurotoxicity among pediatric and aged populations. This effect is usually manifested as cognitive impairment such as perioperative neurocognitive disorders. The wide application of sevoflurane and isoflurane during general anesthesia makes their safety a major health concern. Evidence indicates that iron dyshomeostasis and ferroptosis may establish a role in neurotoxicity of sevoflurane and isoflurane. However, the mechanisms of sevoflurane‐ and isoflurane‐induced neuronal injury were not fully understood, which poses a barrier to the treatment of its neurotoxicity. We, therefore, reviewed the current knowledge on mechanisms of iron dyshomeostasis and ferroptosis and aimed to promote a better understanding of their roles in sevoflurane‐ and isoflurane‐induced neurotoxicity.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Dysregulation of iron homeostasis and ferroptosis in sevoflurane and isoflurane associated perioperative neurocognitive disorders

Miao,

Han,

Wang

et al. 2024

CNS Neurosci Ther

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“…Each year, millions of children undergo anesthesia while undergoing surgical and diagnostic procedures, yet research has unveiled a concerning reality. While it is clear that general anesthesia is necessary for sedation and pain minimization during surgical procedures, the possibility of neurotoxic impairments from its exposure is of concern (Wong-Kee-You et al, 2023). Early exposure to anesthesia may lead to brain damage and learning deficits.…”

Section: Introductionmentioning

confidence: 99%

The Effects of General Anesthesia on Infants and Children's Later Development: A Comprehensive Systematic Review

Nugroho,

Lestari

2024

JLH

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The relationship between pediatric neurodevelopment and general anesthesia has been the subject of numerous investigations, yet consensus remains elusive. Objective: This review aims to explore the connection between anesthesia and child development. We conducted a thorough search of Google Scholar, PubMed, and ProQuest databases from January 2000 until March 2024, using relevant search terms such as “Adolescent,” “Anesthesia, General/ adverse effects,” “Child,” “Child Development / drug effects,” and “Preschool” resulted in 40 out of 1572 studies for reviewed. The review focused on assessing the impact of general anesthesia on children's development, excluding studies involving children with significant comorbidities or lacking unexposed controls. Two coders independently evaluated the studies, adhering to Preferred Reporting Items for Systematic Reviews criteria. Our analysis of 40 primary studies unveiled a broad spectrum of outcomes regarding the impact of general anesthesia on infants and children's subsequent development. Across cognitive domains, anesthesia altered academic achievements, IQ, and language proficiency. Sensory responses were diverse, with anesthesia affecting manual dexterity, balance, and sensory performance uniquely. Psychosocially, it influenced behavior, social skills, and neuropsychological disorders, while neurodevelopmental concerns were also identified. In summary, the effects of general anesthesia on various developmental domains underscore the need for cautious consideration in medical practice. This review revealed cognitive decline, diverse sensory impacts, and increased behavioral issues, anxiety, and neurodevelopmental disorders associated with general anesthesia. Understanding these effects is crucial for implementing effective prevention and management strategies to mitigate long-term complications.

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“…The long-term effects of general anesthetics on functional brain development have become a global public health concern ( Servick, 2014 ) Early childhood marks the most important period for nervous system development, during which time children are most vulnerable to the effects of general anesthetics ( Lee et al, 2015 ; Qiu et al, 2016 ). There is a clear link between anesthesia and abnormal development of the central nervous system ( Wong-Kee-You et al, 2023 ). Therefore, elucidating the biological mechanisms related to these neurodevelopmental abnormalities and developing corresponding brain protection strategies are of great importance for healthy brain development in children.…”

Section: Introductionmentioning

confidence: 99%

Integrated ribosome and proteome analyses reveal insights into sevoflurane-induced long-term social behavior and cognitive dysfunctions through ADNP inhibition in neonatal mice

Liang,

Liu,

Cao

et al. 2024

Zoological Research

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A growing number of studies have demonstrated that repeated exposure to sevoflurane during development results in persistent social abnormalities and cognitive impairment. Davunetide, an active fragment of the activity-dependent neuroprotective protein (ADNP), has been implicated in social and cognitive protection. However, the potential of davunetide to attenuate social deficits following sevoflurane exposure and the underlying developmental mechanisms remain poorly understood. In this study, ribosome and proteome profiles were analyzed to investigate the molecular basis of sevoflurane-induced social deficits in neonatal mice. The neuropathological basis was also explored using Golgi staining, morphological analysis, western blotting, electrophysiological analysis, and behavioral analysis. Results indicated that ADNP was significantly down-regulated following developmental exposure to sevoflurane. In adulthood, anterior cingulate cortex (ACC) neurons exposed to sevoflurane exhibited a decrease in dendrite number, total dendrite length, and spine density. Furthermore, the expression levels of Homer, PSD95, synaptophysin, and vglut2 were significantly reduced in the sevoflurane group. Patch-clamp recordings indicated reductions in both the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs). Notably, davunetide significantly ameliorated the synaptic defects, social behavior deficits, and cognitive impairments induced by sevoflurane. Mechanistic analysis revealed that loss of ADNP led to dysregulation of Ca 2+ activity via the Wnt/β-catenin signaling, resulting in decreased expression of synaptic proteins. Suppression of Wnt signaling was restored in the davunetide-treated group. Thus, ADNP was identified as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general anesthetics. This study provides important insights into the mechanisms underlying social and cognitive disturbances caused by sevoflurane exposure in neonatal mice and elucidates the regulatory pathways involved.

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The impact of early exposure to general anesthesia on visual and neurocognitive development

Cited by 5 publications

References 146 publications

Dysregulation of iron homeostasis and ferroptosis in sevoflurane and isoflurane associated perioperative neurocognitive disorders

Dysregulation of iron homeostasis and ferroptosis in sevoflurane and isoflurane associated perioperative neurocognitive disorders

The Effects of General Anesthesia on Infants and Children's Later Development: A Comprehensive Systematic Review

Integrated ribosome and proteome analyses reveal insights into sevoflurane-induced long-term social behavior and cognitive dysfunctions through ADNP inhibition in neonatal mice

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