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Effects of Sevoflurane on the Development of a Human Brain Microphysiological System
Qun Li1, Lixuan Ding2, Itzy E Morales Pantoja1
1Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
International Journal of Molecular Sciences
|April 14, 2026
Summary
Early exposure to sevoflurane (SEV) anesthesia in a human brain model disrupts neural development, increasing cell death and impairing synapse formation. The mammalian target of rapamycin (mTOR) pathway appears involved in these effects.
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- Animal studies suggest early anesthetic exposure may harm brain development.
- Human implications of early anesthetic exposure on brain development are not fully understood.
Purpose of the Study:
- To investigate the effects of early sevoflurane (SEV) exposure on human brain development using a human brain microphysiological system (bMPS).
Main Methods:
- Human induced pluripotent stem cells (iPSCs) were differentiated into bMPS.
- bMPS were exposed to sevoflurane (SEV) at week 8.
- Immunofluorescence, Western blotting, and qPCR were used to assess neural alterations post-exposure.
Main Results:
- SEV exposure increased apoptotic cells and decreased neural differentiation markers.
- Reduced ratios of mature neurons and oligodendrocytes led to decreased myelination.
- SEV impaired astrocyte development, synaptogenesis (especially excitatory synapses), and activated the mTOR pathway.
Conclusions:
- Early SEV exposure significantly disrupts human brain tissue development.
- The mammalian target of rapamycin (mTOR) signaling pathway is implicated in SEV-induced neurodevelopmental alterations.
