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Effects of Sevoflurane on the Development of a Human Brain Microphysiological System
by
Mintz, Cyrus David
, Morales Pantoja, Itzy E.
, Li, Qun
, Smirnova, Lena
, Modiri, Navid
, Ding, Lixuan
in
Analysis
/ Anesthetics
/ Apoptosis
/ Astrocytes - drug effects
/ Astrocytes - metabolism
/ Brain
/ Brain - cytology
/ Brain - drug effects
/ Brain - growth & development
/ Brain - metabolism
/ Cell Differentiation - drug effects
/ Cells, Cultured
/ Humans
/ Induced Pluripotent Stem Cells - cytology
/ Induced Pluripotent Stem Cells - drug effects
/ Induced Pluripotent Stem Cells - metabolism
/ Medical research
/ Medicine, Experimental
/ Microphysiological Systems
/ Microscopy
/ Neural Stem Cells - cytology
/ Neural Stem Cells - drug effects
/ Neural Stem Cells - metabolism
/ Neurodevelopment
/ Neurogenesis
/ Neurogenesis - drug effects
/ Neurons
/ Neurons - drug effects
/ Neurons - metabolism
/ Neurotoxicity
/ Oligodendroglia - cytology
/ Oligodendroglia - drug effects
/ Oligodendroglia - metabolism
/ Prenatal development
/ Sevoflurane
/ Sevoflurane - adverse effects
/ Sevoflurane - pharmacology
/ Signal Transduction - drug effects
/ Stem cells
/ Surgery
/ TOR Serine-Threonine Kinases - metabolism
2026
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Effects of Sevoflurane on the Development of a Human Brain Microphysiological System
by
Mintz, Cyrus David
, Morales Pantoja, Itzy E.
, Li, Qun
, Smirnova, Lena
, Modiri, Navid
, Ding, Lixuan
in
Analysis
/ Anesthetics
/ Apoptosis
/ Astrocytes - drug effects
/ Astrocytes - metabolism
/ Brain
/ Brain - cytology
/ Brain - drug effects
/ Brain - growth & development
/ Brain - metabolism
/ Cell Differentiation - drug effects
/ Cells, Cultured
/ Humans
/ Induced Pluripotent Stem Cells - cytology
/ Induced Pluripotent Stem Cells - drug effects
/ Induced Pluripotent Stem Cells - metabolism
/ Medical research
/ Medicine, Experimental
/ Microphysiological Systems
/ Microscopy
/ Neural Stem Cells - cytology
/ Neural Stem Cells - drug effects
/ Neural Stem Cells - metabolism
/ Neurodevelopment
/ Neurogenesis
/ Neurogenesis - drug effects
/ Neurons
/ Neurons - drug effects
/ Neurons - metabolism
/ Neurotoxicity
/ Oligodendroglia - cytology
/ Oligodendroglia - drug effects
/ Oligodendroglia - metabolism
/ Prenatal development
/ Sevoflurane
/ Sevoflurane - adverse effects
/ Sevoflurane - pharmacology
/ Signal Transduction - drug effects
/ Stem cells
/ Surgery
/ TOR Serine-Threonine Kinases - metabolism
2026
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Effects of Sevoflurane on the Development of a Human Brain Microphysiological System
by
Mintz, Cyrus David
, Morales Pantoja, Itzy E.
, Li, Qun
, Smirnova, Lena
, Modiri, Navid
, Ding, Lixuan
in
Analysis
/ Anesthetics
/ Apoptosis
/ Astrocytes - drug effects
/ Astrocytes - metabolism
/ Brain
/ Brain - cytology
/ Brain - drug effects
/ Brain - growth & development
/ Brain - metabolism
/ Cell Differentiation - drug effects
/ Cells, Cultured
/ Humans
/ Induced Pluripotent Stem Cells - cytology
/ Induced Pluripotent Stem Cells - drug effects
/ Induced Pluripotent Stem Cells - metabolism
/ Medical research
/ Medicine, Experimental
/ Microphysiological Systems
/ Microscopy
/ Neural Stem Cells - cytology
/ Neural Stem Cells - drug effects
/ Neural Stem Cells - metabolism
/ Neurodevelopment
/ Neurogenesis
/ Neurogenesis - drug effects
/ Neurons
/ Neurons - drug effects
/ Neurons - metabolism
/ Neurotoxicity
/ Oligodendroglia - cytology
/ Oligodendroglia - drug effects
/ Oligodendroglia - metabolism
/ Prenatal development
/ Sevoflurane
/ Sevoflurane - adverse effects
/ Sevoflurane - pharmacology
/ Signal Transduction - drug effects
/ Stem cells
/ Surgery
/ TOR Serine-Threonine Kinases - metabolism
2026
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Effects of Sevoflurane on the Development of a Human Brain Microphysiological System
Journal Article
Effects of Sevoflurane on the Development of a Human Brain Microphysiological System
2026
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Overview
Animal studies have shown that early life exposure to general anesthetics may impair brain development. However, the implications of this phenomenon in human patients remain unclear. In this study, we use an induced pluripotent stem cell (iPSC)-derived human brain microphysiological system (bMPS) to investigate the effects of early sevoflurane (SEV) exposure on human brain development. Human iPSCs were cultured and differentiated into neural progenitor cells (NPCs) and then into bMPS. At week 8, bMPSs were exposed to 2.4% SEV for 4 h. Four weeks after exposure, immunofluorescence (IF), Western blotting (WB), and quantitative real-time polymerase chain reaction (qPCR) were conducted to evaluate the alteration of nerve cells in bMPS. After SEV exposure, the number of apoptotic cells increases, and the level of neural differentiation markers decreases. The ratios of mature neurons over NPCs and mature oligodendrocytes over oligodendrocyte progenitor cells (OPCs) are reduced, which leads to a reduction in myelination. SEV also impedes the development of astrocytes and synaptogenesis, especially the formation of excitatory synapses. Meanwhile, SEV increases the expression of molecules in the mammalian target of rapamycin (mTOR) signal pathway. In conclusion, early SEV exposure substantially disrupts the development of human brain tissue, and the mTOR signal pathway is likely to be involved in this alteration.
Publisher
MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
Subject
/ Brain
/ Brain - growth & development
/ Cell Differentiation - drug effects
/ Humans
/ Induced Pluripotent Stem Cells - cytology
/ Induced Pluripotent Stem Cells - drug effects
/ Induced Pluripotent Stem Cells - metabolism
/ Neural Stem Cells - cytology
/ Neural Stem Cells - drug effects
/ Neural Stem Cells - metabolism
/ Neurons
/ Oligodendroglia - drug effects
/ Oligodendroglia - metabolism
/ Sevoflurane - adverse effects
/ Signal Transduction - drug effects
/ Surgery
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