Somatostatin and its receptors involvement in sevoflurane-induced neurotoxicity: a narrative review

Somatostatin and its receptors involvement in sevoflurane-induced neurotoxicity: a narrative review

Abstract As a widely used pediatric anesthetic, sevoflurane presents a paradoxical neurodevelopmental risk during vulnerable brain maturation periods. This review synthesizes emerging evidence on sevoflurane-induced developmental neurotoxicity, with a focus on somatostatin (SST)-SSTR4 signaling and...

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Main Authors: Yixuan Niu, Jinnan Xu, Yanyong Cheng, Linhong Zhong, Jing Wang, Yanan Jiang, Chen Wang, Zhengjie Miao, Fan Wang, Chuanyu Qi, Tiannan Chen, Yi Gao, Hong Jiang, Jia Yan
Format: Article
Language:English
Published: BMC 2025-08-01
Series:BMC Anesthesiology
Subjects:
Sevoflurane
Developmental neurotoxicity
SST
SSTR4
Synaptic plasticity
Online Access:https://doi.org/10.1186/s12871-025-03242-4
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Summary:Abstract As a widely used pediatric anesthetic, sevoflurane presents a paradoxical neurodevelopmental risk during vulnerable brain maturation periods. This review synthesizes emerging evidence on sevoflurane-induced developmental neurotoxicity, with a focus on somatostatin (SST)-SSTR4 signaling and its downstream effects on synaptic integrity. Key findings reveal that sevoflurane exposure disrupts excitatory-inhibitory balance by upregulating hippocampal SST expression, suppressing glutamatergic synaptic markers (vesicular glutamate transporter 1 (vGLUT1), PSD95), and impairing cAMP/PKA signaling—a pathway essential for AMPA receptor trafficking and synaptic plasticity. Mechanistically, SSTR4 activation exacerbates synaptic dysfunction through adenylate cyclase (AC) inhibition, reducing cAMP levels and diminishing AMPA receptor phosphorylation. Primate and rodent models corroborate these effects, linking SST-SSTR4 dysregulation to long-term cognitive deficits. Single-nucleus RNA sequencing in macaques further identifies altered synaptic development genes after sevoflurane exposure. While preclinical data suggest SSTR4 modulation as a therapeutic target, causal relationships between sevoflurane, SSTergic signaling, and synaptic pathology remain unconfirmed. This work underscores the urgency of refining pediatric anesthesia protocols and developing neuroprotective strategies targeting the SST-SSTR4-cAMP/PKA axis. Future research should prioritize spatiotemporal profiling of SST dynamics, validation of SSTR4-specific interventions, and translational studies using non-human primate models to bridge mechanistic insights with clinical outcomes.
ISSN:1471-2253

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