Bumetanide attenuates sevoflurane‐induced neuroapoptosis in the developing dentate gyrus and impaired behavior in the contextual fear discrimination learning test

Wei, Kai; Liu, Yiheng; Yang, Xiamin; Liu, Jin; Li, Yuan; Deng, Mengying; Wang, Ying Wei

doi:10.1002/brb3.2768

Cited by 4 publications

(2 citation statements)

References 45 publications

(56 reference statements)

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“…On the other hand, Bumetanide has been found to decrease the excitotoxic response of neurons due to its blocking effect on the NKCC1 channel (20). Interestingly, other drugs with neuroprotective properties, such as lithium, melatonin, estrogen, erythropoietin, estradiol, and dexmedetomidine, have demonstrated protective effects in animals against the neurotoxic effect of general anesthetics (21).…”

Section: Effects On Chloride Cotransportersmentioning

confidence: 99%

Cellular Mechanisms Associated with Neurodevelopmental Alterations Produced by General Anesthetics

Trujillo Mejia,

Herrera Gomez

2024

J Cell Mol Anesth

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: There is concern about neurodevelopmental disturbances associated with exposure to general anesthesia during early childhood. In 2016, the U.S. Food and Drug Administration released a safety alert regarding the use of gamma-aminobutyric acid (GABA) agonists and N-methyl-D-aspartate (NMDA) receptor antagonists in pediatric anesthesia, warning about the risks of their use during the last trimester of pregnancy and in children under 3 years for neurodevelopment. Animal and in vitro studies demonstrate worrisome morphological and functional alterations in young neurons and glia induced by different anesthetic drugs. These drugs can induce changes in various neuronal transmission systems, alter dendritic growth and brain connectivity, and initiate processes leading to cell demise, such as aberrant cell cycle reentry, mitochondrial dysfunction, excitotoxicity, neuroapoptosis, disruption of cytoskeletal assembly, and dysregulation of brain-derived neurotrophic factor (BNDF). Additionally, they can generate epigenetic changes that can be transmitted intergenerationally. These effects are related to age, dose, number of anesthetics received, and duration of exposure to said drugs and can be reversible or permanent, caused by direct or indirect perturbations on neurons. These disturbances may manifest as neurodevelopmental disorders later in life. This work aimed to review the cellular mechanisms involved in these alterations.

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Section: Effects On Chloride Cotransportersmentioning

confidence: 99%

Cellular Mechanisms Associated with Neurodevelopmental Alterations Produced by General Anesthetics

Trujillo Mejia,

Herrera Gomez

2024

J Cell Mol Anesth

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“…Lactate accumulation can induce neuronal apoptosis or even acidosis in critically ill patients [24][25][26]. Sevoflurane was shown to activate gamma-aminobutyric acid subtype A receptor (GABAAR) to induce apoptosis of immature dentate granule cells in mice [27]. Apoptosis is regulated by multiple pathways, among which the mechanism of neuronal apoptosis induced by sevoflurane through related signaling pathways has attracted increased attention [28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Sevoflurane upregulates neuron death process-related Ddit4 expression by NMDAR in the hippocampus

Li,

Hou,

Wang

et al. 2023

Aging

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Postoperative cognitive dysfunction (POCD) is a serious and common complication induced by anesthesia and surgery. Neuronal apoptosis induced by general anesthetic neurotoxicity is a high-risk factor. However, a comprehensive analysis of general anesthesia-regulated gene expression patterns and further research on molecular mechanisms are lacking. Here, we performed bioinformatics analysis of gene expression in the hippocampus of aged rats that received sevoflurane anesthesia in GSE139220 from the GEO database, found a total of 226 differentially expressed genes (DEGs) and investigated hub genes according to the number of biological processes in which the genes were enriched and performed screening by 12 algorithms with cytoHubba in Cytoscape. Among the screened hub genes, Agt , Cdkn1a , Ddit4 , and Rhob are related to the neuronal death process. We further confirmed that these genes, especially Ddit4 , were upregulated in the hippocampus of aged mice that received sevoflurane anesthesia. NMDAR , the core target receptor of sevoflurane, rather than GABA A R , mediates the sevoflurane regulation of DDIT4 expression. Our study screened sevoflurane-regulated DEGs and focused on the neuronal death process to reveal DDIT4 as a potential target mediated by NMDAR , which may provide a new target for the treatment of sevoflurane neurotoxicity.

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Bumetanide attenuates sevoflurane‐induced neuroapoptosis in the developing dentate gyrus and impaired behavior in the contextual fear discrimination learning test

et al. 2022

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Introduction: Sevoflurane acts as a gamma-aminobutyric acid subtype A receptor agonist and can induce widespread apoptosis of immature dentate granule cells in postnatal day 21 mice. The dentate granule cells of postnatal day 21 mice undergo a developmental stage when gamma-aminobutyric acid (GABA) shifts from inducing the depolarization of neurons to causing hyperpolarization. However, it is unclear whether sevoflurane induces apoptosis of immature granule cells by facilitating the depolarization or hyperpolarization of neurons. Methods:We utilized bumetanide, an Na + -K + -2Cl − cotransporter isoform 1 (NKCC1) antagonist, to determine whether the NKCC1-mediated GABA depolarization of neurons plays a role in sevoflurane-induced neuroapoptosis. We also investigated whether sevoflurane exposure is related to long-term cognitive dysfunction in postnatal day 21 mice and explored the possible protective effects of bumetanide.Results: Bumetanide attenuated the sevoflurane-induced apoptosis of dentate granule cells in postnatal day 21 mice. Exposure to sevoflurane at postnatal day 21 mice did not affect their motor ability or anxiety level, and it had no effect on spatial learning or memory functions. However, sevoflurane exposure at postnatal day 21 impaired the pattern separation ability in the contextual fear discrimination test; bumetanide mitigated this effect of sevoflurane as well. Conclusion:Bumetanide attenuates sevoflurane-induced apoptosis and is a promising prospect for protecting against anesthesia-induced neurotoxicity in the developing brain.

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Bumetanide attenuates sevoflurane‐induced neuroapoptosis in the developing dentate gyrus and impaired behavior in the contextual fear discrimination learning test

Cited by 4 publications

References 45 publications

Cellular Mechanisms Associated with Neurodevelopmental Alterations Produced by General Anesthetics

Cellular Mechanisms Associated with Neurodevelopmental Alterations Produced by General Anesthetics

Sevoflurane upregulates neuron death process-related Ddit4 expression by NMDAR in the hippocampus

Bumetanide attenuates sevoflurane‐induced neuroapoptosis in the developing dentate gyrus and impaired behavior in the contextual fear discrimination learning test

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