Intravenous anesthetic-induced calcium dysregulation and neurotoxic shift with age during development in primary cultured neurons

Shibuta, Satoshi; Morita, Tomotaka; Kosaka, Jun

doi:10.1016/j.neuro.2018.08.002

Cited by 3 publications

(12 citation statements)

References 56 publications

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“…Trypsin was purchased from Difco Lab (Detroit, MI, USA), fetal calf serum (FCS) from ICN Biochemicals (Costa Mesa, CA, USA), and B-27 Fluo4-AM from Dojindo (Kumamoto, Japan). PPF concentrations in the present study are comparable to the moderate concentrations prescribed for clinical use [9,17].…”

Section: Chemical Reagentssupporting

confidence: 79%

“…PPF-induced neurotoxicity in immature neurons has been previously illustrated [2][3][4][5][6][7][8][9], where, in one of the reports, we have demonstrated that at clinically relevant concentrations, PPF induced a significant increase in intracellular calcium ([Ca 2 + ]i) and neural cell death during the developmental period in rats. Recently, several animal studies have attempted to attenuate PPF-induced neurotoxicity [10][11][12].…”

Section: Introductionmentioning

confidence: 56%

“…We calculated HR and SR to minimize the effect of various conditions associated with primary culture, including temperature, vehicle, and the concentration of sevoflurane used after the removal of fetuses. HR and SR factors were used for the comparison of groups as these conditions were the same in the sister-control culture dishes [9,23,24]. Statistical comparisons for the number of cells whose Fmax exceeded 1.5, HR, and SR were conducted using JMP Pro 1 13.2.0 software (SAS Insti.…”

Section: Discussionmentioning

confidence: 99%

“…Calcium imaging experiments were conducted as previously described [9,[22][23][24]. On DIV 4, the intracellular calcium concentration ([Ca 2+ ]i) was measured using a fluorescence measurement system (Aquacosmos 1 ; Hamamatsu Photonics, Hamamatsu, Japan) and an inverted phase contrast microscope (Axiovert 200 1 ; Carl Zeiss, Oberkochen, Germany).…”

Section: Calcium Imaging Experimentsmentioning

confidence: 99%

“…PPF solution was administered by a second observer blinded to the study design and treatment protocols on the areas near the observed neurons, but not directly onto the cells, using a P-200 Gilson Pipetman with a maximum effective volume of 50 μl (final volume of 1 ml solution: 10 or 100 μM PPF) as reported previously [9,23].…”

Section: Plos Onementioning

confidence: 99%

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Effect of preconditioning on propofol-induced neurotoxicity during the developmental period

Shibuta

Morita²,

Kosaka³

2022

PLoS ONE

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At therapeutic concentrations, propofol (PPF), an anesthetic agent, significantly elevates intracellular calcium concentration ([Ca2 +]i) and induces neural death during the developmental period. Preconditioning enables specialized tissues to tolerate major insults better compared with tissues that have already been exposed to sublethal insults. Here, we investigated whether the neurotoxicity induced by clinical concentrations of PPF could be alleviated by prior exposure to sublethal amounts of PPF. Cortical neurons from embryonic day (E) 17 Wistar rat fetuses were cultured in vitro, and on day in vitro (DIV) 2, the cells were preconditioned by exposure to PPF (PPF-PC) at either 100 nM or 1 μM for 24 h. For morphological observations, cells were exposed to clinical concentrations of PPF (10 μM or 100 μM) for 24 h and the survival ratio (SR) was calculated. Calcium imaging revealed significant PPF-induced [Ca2+]i elevation in cells on DIV 4 regardless of PPF-PC. Additionally, PPF-PC did not alleviate neural cell death induced by PPF under any condition. Our findings indicate that PPF-PC does not alleviate PPF-induced neurotoxicity during the developmental period.

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Section: Chemical Reagentssupporting

confidence: 79%

Section: Introductionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Calcium Imaging Experimentsmentioning

confidence: 99%

Section: Plos Onementioning

confidence: 99%

See 3 more Smart Citations

Effect of preconditioning on propofol-induced neurotoxicity during the developmental period

Shibuta

Morita²,

Kosaka³

2022

PLoS ONE

Self Cite

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Anaesthesia and brain development: a review of propofol-induced neurotoxicity in pediatric populations

Zhang,

Liu,

Wang

et al. 2024

J Dev Orig Health Dis

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With the advancement of medical technology, there are increasing opportunities for new-borns, infants, and pregnant women to be exposed to general anaesthesia. Propofol is commonly used for the induction of anaesthesia, maintenance of general intravenous anaesthesia and sedation of intensive-care children. Many previous studies have found that propofol has organ-protective effects, but growing evidence suggests that propofol interferes with brain development, affecting learning and cognitive function. The purpose of this review is to summarize the latest progress in understanding the neurotoxicity of propofol. Evidence from case studies and clinical studies suggests that propofol has neurotoxicity on the developing brain. We classify the findings on propofol-induced neurotoxicity based on its damage mechanism. We end by summarizing the current protective strategies against propofol neurotoxicity. Fully understanding the neurotoxic mechanisms of propofol can help us use it at a reasonable dosage, reduce its side effects, and increase patient safety.

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The potential value of exosomes as adjuvants for novel biologic local anesthetics

et al. 2023

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The side effects of anesthetic drugs are a key preoperative concern for anesthesiologists. Anesthetic drugs used for general anesthesia and regional blocks are associated with a potential risk of systemic toxicity. This prompted the use of anesthetic adjuvants to ameliorate these side effects and improve clinical outcomes. However, the adverse effects of anesthetic adjuvants, such as neurotoxicity and gastrointestinal reactions, have raised concerns about their clinical use. Therefore, the development of relatively safe anesthetic adjuvants with fewer side effects is an important area for future anesthetic drug research. Exosomes, which contain multiple vesicles with genetic information, can be released by living cells with regenerative and specific effects. Exosomes released by specific cell types have been found to have similar effects as many local anesthetic adjuvants. Due to their biological activity, carrier efficacy, and ability to repair damaged tissues, exosomes may have a better efficacy and safety profile than the currently used anesthetic adjuvants. In this article, we summarize the contemporary literature about local anesthetic adjuvants and highlight their potential side effects, while discussing the potential of exosomes as novel local anesthetic adjuvant drugs.

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Intravenous anesthetic-induced calcium dysregulation and neurotoxic shift with age during development in primary cultured neurons

Cited by 3 publications

References 56 publications

Effect of preconditioning on propofol-induced neurotoxicity during the developmental period

Effect of preconditioning on propofol-induced neurotoxicity during the developmental period

Anaesthesia and brain development: a review of propofol-induced neurotoxicity in pediatric populations

The potential value of exosomes as adjuvants for novel biologic local anesthetics

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