Assessing potential desflurane-induced neurotoxicity using nonhuman primate neural stem cell models
Safety concerns about general anesthetics (GA), such as desflurane (a commonly used gaseous anesthetic agent), arose from studies documenting neural cell death and behavioral changes after early-life exposure to anesthetics and compounds with related modes of action. Neural stem cells (NSCs) can rec...
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| Format: | Article |
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Frontiers Media S.A.
2025-06-01
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| Series: | Experimental Biology and Medicine |
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| Online Access: | https://www.ebm-journal.org/articles/10.3389/ebm.2025.10606/full |
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| author | Cheng Wang Leah E. Latham Shuliang Liu John Talpos Tucker A. Patterson Joseph P. Hanig Fang Liu |
| author_facet | Cheng Wang Leah E. Latham Shuliang Liu John Talpos Tucker A. Patterson Joseph P. Hanig Fang Liu |
| author_sort | Cheng Wang |
| collection | DOAJ |
| description | Safety concerns about general anesthetics (GA), such as desflurane (a commonly used gaseous anesthetic agent), arose from studies documenting neural cell death and behavioral changes after early-life exposure to anesthetics and compounds with related modes of action. Neural stem cells (NSCs) can recapitulate most critical events during central nervous system (CNS) development in vivo and, therefore, represent a valuable in vitro model for evaluating potential desflurane-induced developmental neurotoxicity. In this study, NSCs harvested from the hippocampus of a gestational day 80 monkey brain were applied to explore the temporal relationships between desflurane exposures and neural stem cell health, proliferation, differentiation, and viability. At clinically relevant doses (5.7%), desflurane exposure did not result in significant changes in NSC viability [lactate dehydrogenase (LDH) release] and NSC proliferation profile/rate by Cell Cycle Assay, in both short term (3 h) and prolonged (24 h) exposure groups. However, when monkey NSCs were guided to differentiate into neural cells (including neurons, astrocytes, and oligodendrocytes), and then exposed to desflurane (5.7%), no significant changes were detected in LDH release after a 3-h exposure, but a significant elevation in LDH release into the culture medium was observed after a 24-h exposure. Desflurane (24 h)-induced neural damage was further supported by increased expression levels of multiple cytokines, e.g., G-CSF, IL-12, IL-9, IL-10, and TNF-α compared with the controls. Additionally, our immunocytochemistry and flow cytometry data demonstrated a remarkable attenuation of differentiated neurons as evidenced by significantly decreased numbers of polysialic acid neural cell adhesion molecule (PSA-NCAM)-positive cells in the desflurane-exposed (prolonged) cultures. Our data suggests that at the clinically relevant concentration, desflurane did not induce NSC damage/death, but impaired the differentiated neuronal cells after prolonged exposure. Collectively, PSA-NCAM could be essential for neuronal viability. Desflurane-induced neurotoxicity was primarily associated with the loss of differentiated neurons. Changes in the neuronal specific marker, PSA-NCAM, may help understand the underlying mechanisms associated with anesthetic-induced neuronal damage. These findings should be helpful/useful for the understanding of the diverse effects of desflurane exposure on the developing brain and could be used to optimize the usage of these agents in the pediatric setting. |
| format | Article |
| id | doaj-art-e61d78a6e0464ce0acafa20ac83e75da |
| institution | Kabale University |
| issn | 1535-3699 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Experimental Biology and Medicine |
| spelling | doaj-art-e61d78a6e0464ce0acafa20ac83e75da2025-08-20T03:45:07ZengFrontiers Media S.A.Experimental Biology and Medicine1535-36992025-06-0125010.3389/ebm.2025.1060610606Assessing potential desflurane-induced neurotoxicity using nonhuman primate neural stem cell modelsCheng Wang0Leah E. Latham1Shuliang Liu2John Talpos3Tucker A. Patterson4Joseph P. Hanig5Fang Liu6Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, United StatesDivision of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, United StatesDivision of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, United StatesDivision of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, United StatesOffice of Center Director, National Center for Toxicological Research/Food and Drug Administration (FDA), Jefferson, AR, United StatesOffice of Pharmaceutical Quality, Center for Drug Evaluation and Research/FDA, Silver Spring, MD, United StatesDivision of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, United StatesSafety concerns about general anesthetics (GA), such as desflurane (a commonly used gaseous anesthetic agent), arose from studies documenting neural cell death and behavioral changes after early-life exposure to anesthetics and compounds with related modes of action. Neural stem cells (NSCs) can recapitulate most critical events during central nervous system (CNS) development in vivo and, therefore, represent a valuable in vitro model for evaluating potential desflurane-induced developmental neurotoxicity. In this study, NSCs harvested from the hippocampus of a gestational day 80 monkey brain were applied to explore the temporal relationships between desflurane exposures and neural stem cell health, proliferation, differentiation, and viability. At clinically relevant doses (5.7%), desflurane exposure did not result in significant changes in NSC viability [lactate dehydrogenase (LDH) release] and NSC proliferation profile/rate by Cell Cycle Assay, in both short term (3 h) and prolonged (24 h) exposure groups. However, when monkey NSCs were guided to differentiate into neural cells (including neurons, astrocytes, and oligodendrocytes), and then exposed to desflurane (5.7%), no significant changes were detected in LDH release after a 3-h exposure, but a significant elevation in LDH release into the culture medium was observed after a 24-h exposure. Desflurane (24 h)-induced neural damage was further supported by increased expression levels of multiple cytokines, e.g., G-CSF, IL-12, IL-9, IL-10, and TNF-α compared with the controls. Additionally, our immunocytochemistry and flow cytometry data demonstrated a remarkable attenuation of differentiated neurons as evidenced by significantly decreased numbers of polysialic acid neural cell adhesion molecule (PSA-NCAM)-positive cells in the desflurane-exposed (prolonged) cultures. Our data suggests that at the clinically relevant concentration, desflurane did not induce NSC damage/death, but impaired the differentiated neuronal cells after prolonged exposure. Collectively, PSA-NCAM could be essential for neuronal viability. Desflurane-induced neurotoxicity was primarily associated with the loss of differentiated neurons. Changes in the neuronal specific marker, PSA-NCAM, may help understand the underlying mechanisms associated with anesthetic-induced neuronal damage. These findings should be helpful/useful for the understanding of the diverse effects of desflurane exposure on the developing brain and could be used to optimize the usage of these agents in the pediatric setting.https://www.ebm-journal.org/articles/10.3389/ebm.2025.10606/fullanestheticsdesflurane,developing neuronsneural differentiationneurotoxicity |
| spellingShingle | Cheng Wang Leah E. Latham Shuliang Liu John Talpos Tucker A. Patterson Joseph P. Hanig Fang Liu Assessing potential desflurane-induced neurotoxicity using nonhuman primate neural stem cell models Experimental Biology and Medicine anesthetics desflurane, developing neurons neural differentiation neurotoxicity |
| title | Assessing potential desflurane-induced neurotoxicity using nonhuman primate neural stem cell models |
| title_full | Assessing potential desflurane-induced neurotoxicity using nonhuman primate neural stem cell models |
| title_fullStr | Assessing potential desflurane-induced neurotoxicity using nonhuman primate neural stem cell models |
| title_full_unstemmed | Assessing potential desflurane-induced neurotoxicity using nonhuman primate neural stem cell models |
| title_short | Assessing potential desflurane-induced neurotoxicity using nonhuman primate neural stem cell models |
| title_sort | assessing potential desflurane induced neurotoxicity using nonhuman primate neural stem cell models |
| topic | anesthetics desflurane, developing neurons neural differentiation neurotoxicity |
| url | https://www.ebm-journal.org/articles/10.3389/ebm.2025.10606/full |
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