Sevoflurane aggravates hypoxic-ischemic encephalopathy in preterm neonates via VGluT1 upregulation and myelinogenesis impairment
Sevoflurane, a widely used volatile anesthetic, has been associated with neurodevelopmental impairments in neonates, particularly in the context of hypoxic-ischemic (HI) brain injury. In this study, we investigated the effects of sevoflurane exposure on cognitive function and myelination using a pre...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-09-01
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| Series: | Brain Research Bulletin |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S036192302500262X |
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| Summary: | Sevoflurane, a widely used volatile anesthetic, has been associated with neurodevelopmental impairments in neonates, particularly in the context of hypoxic-ischemic (HI) brain injury. In this study, we investigated the effects of sevoflurane exposure on cognitive function and myelination using a preterm white matter injury (WMI) mouse model. Postnatal day 3 (P3) mice underwent HI induction followed by 3.2 % sevoflurane exposure for 2 h. Behavioral assessments using the Morris water maze (MWM) revealed that sevoflurane significantly exacerbated HI-induced spatial learning and memory deficits. Immunohistochemical and Western blot analyses showed that sevoflurane exposure caused significant reductions in myelin basic protein (MBP) levels and disrupted oligodendrocyte maturation. Mechanistic investigations revealed that sevoflurane upregulated vesicular glutamate transporter 1 (VGluT1) expression in presynaptic neurons, resulting in excessive glutamate release and subsequent overactivation of GluR2-lacking AMPA receptors in oligodendrocyte precursor cells (OPCs). Notably, pharmacological inhibition of VGluT1 with CSB6B effectively attenuated these effects, as evidenced by restored membrane GluR2 expression, reduced extracellular glutamate concentrations, and improved myelination accompanied by better cognitive performance. These collective findings demonstrate that sevoflurane exacerbates HI-induced dysmyelination and cognitive impairment through VGluT1-mediated glutamate dysregulation. This study highlights the importance of considering anesthetic protocols in preterm neonates and identifies VGluT1 as a potential therapeutic target for mitigating WMI-related neurodevelopmental deficits. |
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| ISSN: | 1873-2747 |