1. Whole-brain characterization of apoptosis after sevoflurane anesthesia reveals neuronal cell death patterns in the mouse neonatal neocortex
- Author
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Julie Areias, Chrystelle Sola, Yan Chastagnier, Julien Pico, Nathalie Bouquier, Christophe Dadure, Julie Perroy, and Vivien Szabo
- Subjects
Medicine ,Science - Abstract
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.
- Published
- 2023
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