Whole-brain characterization of apoptosis after sevoflurane anesthesia reveals neuronal cell death patterns in the mouse neonatal neocortex
Abstract In the last two decades, safety concerns about general anesthesia (GA) arose from studies documenting brain cell death in various pharmacological conditions and animal models. Nowadays, a thorough characterization of sevoflurane-induced apoptosis in the entire neonatal mouse brain would hel...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-41750-w |
| _version_ | 1827710936852463616 |
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| author | Julie Areias Chrystelle Sola Yan Chastagnier Julien Pico Nathalie Bouquier Christophe Dadure Julie Perroy Vivien Szabo |
| author_facet | Julie Areias Chrystelle Sola Yan Chastagnier Julien Pico Nathalie Bouquier Christophe Dadure Julie Perroy Vivien Szabo |
| author_sort | Julie Areias |
| collection | DOAJ |
| description | Abstract In the last two decades, safety concerns about general anesthesia (GA) arose from studies documenting brain cell death in various pharmacological conditions and animal models. Nowadays, a thorough characterization of sevoflurane-induced apoptosis in the entire neonatal mouse brain would help identify and further focus on underlying mechanisms. We performed whole-brain mapping of sevoflurane-induced apoptosis in post-natal day (P) 7 mice using tissue clearing and immunohistochemistry. We found an anatomically heterogenous increase in cleaved-caspase-3 staining. The use of a novel P7 brain atlas showed that the neocortex was the most affected area, followed by the striatum and the metencephalon. Histological characterization in cortical slices determined that post-mitotic neurons were the most affected cell type and followed inter- and intracortical gradients with maximal apoptosis in the superficial layers of the posterodorsal cortex. The unbiased anatomical mapping used here allowed us to confirm sevoflurane-induced apoptosis in the perinatal period, neocortical involvement, and indicated striatal and metencephalic damage while suggesting moderate hippocampal one. The identification of neocortical gradients is consistent with a maturity-dependent mechanism. Further research could then focus on the interference of sevoflurane with neuronal migration and survival during development. |
| first_indexed | 2024-03-10T17:46:49Z |
| format | Article |
| id | doaj.art-52c8612ace804849ae5ddbacdf259c52 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T17:46:49Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-52c8612ace804849ae5ddbacdf259c522023-11-20T09:29:20ZengNature PortfolioScientific Reports2045-23222023-09-011311910.1038/s41598-023-41750-wWhole-brain characterization of apoptosis after sevoflurane anesthesia reveals neuronal cell death patterns in the mouse neonatal neocortexJulie Areias0Chrystelle Sola1Yan Chastagnier2Julien Pico3Nathalie Bouquier4Christophe Dadure5Julie Perroy6Vivien Szabo7IGF, University of Montpellier, CNRS, INSERMIGF, University of Montpellier, CNRS, INSERMIGF, University of Montpellier, CNRS, INSERMIGF, University of Montpellier, CNRS, INSERMIGF, University of Montpellier, CNRS, INSERMIGF, University of Montpellier, CNRS, INSERMIGF, University of Montpellier, CNRS, INSERMIGF, University of Montpellier, CNRS, INSERMAbstract In the last two decades, safety concerns about general anesthesia (GA) arose from studies documenting brain cell death in various pharmacological conditions and animal models. Nowadays, a thorough characterization of sevoflurane-induced apoptosis in the entire neonatal mouse brain would help identify and further focus on underlying mechanisms. We performed whole-brain mapping of sevoflurane-induced apoptosis in post-natal day (P) 7 mice using tissue clearing and immunohistochemistry. We found an anatomically heterogenous increase in cleaved-caspase-3 staining. The use of a novel P7 brain atlas showed that the neocortex was the most affected area, followed by the striatum and the metencephalon. Histological characterization in cortical slices determined that post-mitotic neurons were the most affected cell type and followed inter- and intracortical gradients with maximal apoptosis in the superficial layers of the posterodorsal cortex. The unbiased anatomical mapping used here allowed us to confirm sevoflurane-induced apoptosis in the perinatal period, neocortical involvement, and indicated striatal and metencephalic damage while suggesting moderate hippocampal one. The identification of neocortical gradients is consistent with a maturity-dependent mechanism. Further research could then focus on the interference of sevoflurane with neuronal migration and survival during development.https://doi.org/10.1038/s41598-023-41750-w |
| spellingShingle | Julie Areias Chrystelle Sola Yan Chastagnier Julien Pico Nathalie Bouquier Christophe Dadure Julie Perroy Vivien Szabo Whole-brain characterization of apoptosis after sevoflurane anesthesia reveals neuronal cell death patterns in the mouse neonatal neocortex Scientific Reports |
| title | Whole-brain characterization of apoptosis after sevoflurane anesthesia reveals neuronal cell death patterns in the mouse neonatal neocortex |
| title_full | Whole-brain characterization of apoptosis after sevoflurane anesthesia reveals neuronal cell death patterns in the mouse neonatal neocortex |
| title_fullStr | Whole-brain characterization of apoptosis after sevoflurane anesthesia reveals neuronal cell death patterns in the mouse neonatal neocortex |
| title_full_unstemmed | Whole-brain characterization of apoptosis after sevoflurane anesthesia reveals neuronal cell death patterns in the mouse neonatal neocortex |
| title_short | Whole-brain characterization of apoptosis after sevoflurane anesthesia reveals neuronal cell death patterns in the mouse neonatal neocortex |
| title_sort | whole brain characterization of apoptosis after sevoflurane anesthesia reveals neuronal cell death patterns in the mouse neonatal neocortex |
| url | https://doi.org/10.1038/s41598-023-41750-w |
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