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Hypothalamic thermoregulatory neurons divergently modulate isoflurane anesthesia via temperature dependent and independent mechanisms.

Overview

Authors: Shuang Cai1,2,3, Wen Z. Yang4, Mao Xu2,5, Huimin Chen6, Liang Zhou2, Tianyuan Luo2,3, Shouyang Yu2, Kan Zhang1, Haiying Wang3, Tian Yu2,3,5, Jijian Zheng1, Wei L. Shen4,5
ORCID iDs: Shuang Cai
  1. Department of Anesthesiology, Shanghai Children’s Medical Centre, Shanghai Jiao Tong University, Shanghai 200127, China
  2. Key Laboratory of Brain Science, Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (In Cultivation), Zunyi Medical University, Zunyi, Guizhou 563006, China
  3. Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, China
  4. School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
  5. Zunyi Medical University, Zunyi, Guizhou 563006, China
  6. Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China
Journal: iScience, volume 29, issue 5, article 115542
Dates: received 31 October 2025; accepted 26 March 2026; published online 30 March 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.isci.2026.115542 · PMID 42004037 · PMCID PMC13091562 · OpenAlex W7144067344
Open access: gold, a free copy (OpenAlex)
Status: code on request (how the code is found and verified)
Categories: human (organism), systems (subfield)
Methods: Statistics, Spectral & time-frequency, Single-unit activity, calcium imaging, Physiology & signal measures
Keywords: health sciences, human physiology, neuroscience
Topic: Anesthesia and Neurotoxicity Research (Developmental Neuroscience, Neuroscience), according to OpenAlex
Citations: not cited yet (Europe PMC); 52 references in the paper
Research resources: Rabbit anti-c-Fos RRID:AB_2231974, Goat anti-rabbit IgG Alexa Fluor 594 RRID:AB_2307325, Rabbit anti-Glutamate RRID:AB_259946

Abstract

Perioperative hypothermia is common clinically. The neural mechanisms underlying general anesthesia and the hypothermia it induces remain elusive. We found that lower core temperature (Tcore) deepened anesthesia and delayed emergence, which showed a logarithmic relationship below 31.9°C. Chemogenetic activation of brain-derived neurotrophic factor in the lateral preoptic area (LPOBDNF) neurons before isoflurane administration lowered Tcore and increased isoflurane induced burst-suppression ratio (BSR), δ power, and recovery time, while its optogenetic activation during isoflurane did not change Tcore and anesthesia depth. Conversely, chemogenetic activation of dorsomedial hypothalamus glutamatergic (DMHVglut2) neurons increased Tcore, attenuated anesthesia depth and promoted recovery. Stage-specific optogenetic activation of DMHVglut2 neurons and its downstream raphe pallidus (RPa) projection during isoflurane exposure induced cortical activation without Tcore alteration. Our study indicates that LPOBDNF neurons modulate isoflurane anesthesia primarily through temperature-dependent mechanism, while DMHVglut2 neurons and the DMHVglut2 to RPa pathway have a temperature-independent function in modulating isoflurane anesthesia.

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

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

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Data

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Data and code availability

• All data reported in this paper will be shared by the lead contact upon request. • This paper does not report original code. • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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

Versions

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 12 authors, 3 keywords, 3 funders, 52 references, 3 RRIDs.

Cite

This paper

Cai, S., Yang, W. Z., Xu, M., Chen, H., Zhou, L., Luo, T., Yu, S., Zhang, K., Wang, H., Yu, T., Zheng, J., & Shen, W. L. (2026). Hypothalamic thermoregulatory neurons divergently modulate isoflurane anesthesia via temperature dependent and independent mechanisms. iScience, 29(5), 115542. https://doi.org/10.1016/j.isci.2026.115542

BibTeX

@article{cai2026hypothalamic,
author = {Cai, Shuang and Yang, Wen Z. and Xu, Mao and Chen, Huimin and Zhou, Liang and Luo, Tianyuan and Yu, Shouyang and Zhang, Kan and Wang, Haiying and Yu, Tian and Zheng, Jijian and Shen, Wei L.},
title = {{Hypothalamic thermoregulatory neurons divergently modulate isoflurane anesthesia via temperature dependent and independent mechanisms}},
journal = {iScience},
year = {2026},
month = mar,
volume = {29},
number = {5},
pages = {115542},
publisher = {Elsevier},
issn = {2589-0042},
doi = {10.1016/j.isci.2026.115542},
url = {https://doi.org/10.1016/j.isci.2026.115542},
pmid = {42004037},
pmcid = {PMC13091562}
}

RIS

TY - JOUR
AU - Cai, Shuang
AU - Yang, Wen Z.
AU - Xu, Mao
AU - Chen, Huimin
AU - Zhou, Liang
AU - Luo, Tianyuan
AU - Yu, Shouyang
AU - Zhang, Kan
AU - Wang, Haiying
AU - Yu, Tian
AU - Zheng, Jijian
AU - Shen, Wei L.
TI - Hypothalamic thermoregulatory neurons divergently modulate isoflurane anesthesia via temperature dependent and independent mechanisms
T2 - iScience
J2 - iScience
PY - 2026
DA - 2026/03/30
VL - 29
IS - 5
SP - 115542
SN - 2589-0042
PB - Elsevier
DO - 10.1016/j.isci.2026.115542
UR - https://doi.org/10.1016/j.isci.2026.115542
LA - en
ER -

CSL-JSON

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