Sevoflurane ameliorates cerebral ischemia-reperfusion injury by modulating mitochondrial dynamics and attenuating apoptosis via Shh-YAP1 signaling pathway.

Overview

Authors: Li Peng^1,2, Mengmeng Yang^1,2, Jiayuan Liu^1,2, Tianyue Yin^1,2, Jun Li¹, Shuaijie Sun^1,3, Hongrui Zhu¹, Sheng Wang¹

ORCID iDs: Hongrui Zhu

Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 16 Lujiang Road, Hefei City, 230001 Anhui People’s Republic of China
Core Facility Center, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Hefei, 230001 Anhui People’s Republic of China
Department of Anesthesiology, Wannan Medical College, Wuhu, 241002 People’s Republic of China

Institutions: University of Science and Technology of China (China); Anhui Provincial Hospital (China); Wannan Medical College (China)

Journal: Molecular brain, volume 19, issue 1, article 57

Dates: received 27 January 2026; accepted 11 May 2026; published online 21 May 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.1186/s13041-026-01312-3 · PMID 42169018 · PMCID PMC13371202 · OpenAlex W7161994147

Open access: gold, a free copy (OpenAlex)

Status: data only

Categories: histology / microscopy (modality), mouse (organism), stroke (population), cellular / molecular (subfield)

Methods: Preprocessing, Statistics, Single-unit activity, calcium imaging

Keywords: Sevoflurane, Ischemic stroke, Sonic hedgehog, Mitochondrial dynamics, SUMOylation, Apoptosis

MeSH: Adaptor Proteins, Signal Transducing*, Apoptosis*, Brain Ischemia*, Hedgehog Proteins*, Mitochondrial Dynamics*, Reperfusion Injury*, Sevoflurane*, Signal Transduction*, Animals, Calcium, Cell Line, Glucose, Infarction, Middle Cerebral Artery, Male, Mice, Mice, Inbred C57BL, Mitochondria, Neurons, YAP-Signaling Proteins (* major topic)

Topic: Hippo pathway signaling and YAP/TAZ (Cell Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex

Funding: National Natural Science Foundation of China (82272225, 81860249)

Citations: cited by 1 paper (Europe PMC); 57 references in the paper

Research resources: p-Drp1S637 RRID:AB_10622027, t-Drp1 RRID:AB_10659110, β-actin RRID:AB_10700003, Shh RRID:AB_10709580, Fi8 RRID:AB_11149382, YAP1 RRID:AB_1131430, Cle.caspase-3 RRID:AB_2070042, p-Drp1S616 RRID:AB_2085352, GAPDH RRID:AB_2107436, Mfn1 RRID:AB_2142616, MST1 RRID:AB_2144632, Mfn2 RRID:AB_2235195, LATS1 RRID:AB_2296754, SUMO1 RRID:AB_2833449, Caspase-9 RRID:AB_2835042, Pro.Caspase-3 RRID:AB_2835170, RRID:AB_2862646, Gli1 RRID:AB_2934097, OPA1 RRID:AB_3101815, Bax RRID:AB_3698184, SUMO2/3 RRID:AB_3731315, UBC9 RRID:AB_3731317, Bcl-2 RRID:AB_626736, HT22 cells RRID:CVCL_0321, Adult male C57BL/6J RRID:IMSR_JAX:000664

Abstract

Ischemia–reperfusion injury (IRI) is a critical issue in the prevention and treatment of ischemic stroke. Inhalational anesthetics have been proven to have neuroprotective effects and sevoflurane is currently the most commonly used inhaled anesthetic in the clinic. However, the effects and underlying mechanism of sevoflurane on cerebral IRI have not been fully elucidated. In this study, oxygen–glucose deprivation model was established in primary mouse cortical neurons and HT22 cells, while the middle cerebral artery occlusion model was established in mice. Using laser speckle imaging, TTC staining, HE staining, Nissl staining, flow cytometry, calcium imaging and neurologic deficit scoring, we found that sevoflurane post-conditioning (SPC) significantly increased cerebral blood flow, reduced the infarct volume, alleviated neuronal pathological damage, promoted the survival of cortical neurons, reduced cell apoptosis, enhanced calcium responses and decreased the neurologic deficit scores after IRI. The results of RNA sequencing, Western blot, co-immunoprecipitation, TUNEL staining, immunofluorescence, transmission electron microscopy imaging, MPTP measurement, MMP detection, and ATP production measurement showed that the sonic hedgehog (Shh) signaling pathway crosstalk with Hippo-YAP signaling pathway, and the Shh-YAP1 pathway regulated mitochondrial dynamics and mitochondrial ultrastructure and function. In addition, SPC affected the phosphorylation and SUMOylation of dynamin-related protein 1 (Drp1), and there was an interaction between the phosphorylation and SUMOylation of Drp1. In conclusion, this study revealed that SPC might affect the phosphorylation and SUMOylation of Drp1 through the Shh-YAP1 signaling pathway, regulating mitochondrial dynamics, reducing cell apoptosis and ameliorating IRI. These findings offer new insights into the therapeutic strategies for ischemic stroke.

Supplementary Information: The online version contains supplementary material available at 10.1186/s13041-026-01312-3.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

figshare:32989023, at figshare; found in DataCite

Data availability

The research protocols and analysis plans are available in the current manuscript. All study data will be available at time of publication to researchers who provide a methodologically sound and ethically approved proposal, for any purpose of analysis.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 6 keywords, 19 MeSH terms, 1 funder, 57 references, 25 RRIDs.

Cite

This paper

Peng, L., Yang, M., Liu, J., Yin, T., Li, J., Sun, S., Zhu, H., & Wang, S. (2026). Sevoflurane ameliorates cerebral ischemia-reperfusion injury by modulating mitochondrial dynamics and attenuating apoptosis via Shh-YAP1 signaling pathway. Molecular brain, 19(1), 57. https://doi.org/10.1186/s13041-026-01312-3

BibTeX

@article{peng2026sevoflurane, author = {Peng, Li and Yang, Mengmeng and Liu, Jiayuan and Yin, Tianyue and Li, Jun and Sun, Shuaijie and Zhu, Hongrui and Wang, Sheng}, title = {{Sevoflurane ameliorates cerebral ischemia-reperfusion injury by modulating mitochondrial dynamics and attenuating apoptosis via Shh-YAP1 signaling pathway}}, journal = {Molecular brain}, year = {2026}, month = may, volume = {19}, number = {1}, pages = {57}, publisher = {BMC}, issn = {1756-6606}, doi = {10.1186/s13041-026-01312-3}, url = {https://doi.org/10.1186/s13041-026-01312-3}, pmid = {42169018}, pmcid = {PMC13371202} }

RIS

TY - JOUR AU - Peng, Li AU - Yang, Mengmeng AU - Liu, Jiayuan AU - Yin, Tianyue AU - Li, Jun AU - Sun, Shuaijie AU - Zhu, Hongrui AU - Wang, Sheng TI - Sevoflurane ameliorates cerebral ischemia-reperfusion injury by modulating mitochondrial dynamics and attenuating apoptosis via Shh-YAP1 signaling pathway T2 - Molecular brain J2 - Mol Brain PY - 2026 DA - 2026/05/21 VL - 19 IS - 1 SP - 57 SN - 1756-6606 PB - BMC DO - 10.1186/s13041-026-01312-3 UR - https://doi.org/10.1186/s13041-026-01312-3 LA - en ER -

CSL-JSON

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