Evidence map›Paper›PMID 27001149›Full record

ArticleNeurobiology of disease2016

Role of histone acetylation in long-term neurobehavioral effects of neonatal Exposure to sevoflurane in rats.

Min Jia, Wen-Xue Liu, Jiao-Jiao Yang, Ning Xu, Ze-Min Xie, Ling-Sha Ju, Mu-Huo Ji, Anatoly E Martynyuk, Jian-Jun Yang

Open access · greenAbstract read
In one paragraph

Article in Neurobiology of disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.

  1. Dexmedetomidine Mitigates Sevoflurane-Induced Neurodevelopmental Effects in Paediatric Anaesthesia: A Meta-Analysis and Preclinical Study.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026
    Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 2 countries.

Min Jia *Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
Wen-Xue Liu *Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
Jiao-Jiao YangJiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, China.
Ning XuJiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, China.
Ze-Min XieJiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, China.
Ling-Sha JuDepartment of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
Mu-Huo JiDepartment of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
Anatoly E MartynyukDepartment of Anesthesiology, University of Florida, Gainesville, Florida, USA.
Jian-Jun YangDepartment of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
Nanjing General Hospital of Nanjing Military Command · CNNanjing University · CNXuzhou Medical College · CNUniversity of Florida · US

Funding

Role of the limbic-hypothalamic-pituitary-adrenal axis and gamma-aminobutyric acid type A receptor-mediated excitation in the developmental central and systemic effects of neonatal anesthesiaR01NS091542 · NINDS · UNIVERSITY OF FLORIDA · PI MARTYNYUK, ANATOLY E · 2015 to 2018
$1.4M
Mechanism of neurological and cognitive side effects of sevoflurane anesthesia atR01GM093036 · NIGMS · UNIVERSITY OF FLORIDA · PI MARTYNYUK, ANATOLY E · 2011 to 2014
$1.1M
NIGMS NIH HHS R01 GM093036NINDS NIH HHS R01 NS091542
6 · The paper itself

Abstract

Human studies, and especially laboratory studies, provide evidence that early life exposure to general anesthesia may affect neurocognitive development via largely unknown mechanisms. We explored whether hippocampal histone acetylation had a role in neurodevelopmental effects of sevoflurane administered to neonatal rats. Male Sprague-Dawley rats were exposed to 3% sevoflurane or were subjected to maternal separation only for 2h daily at postnatal days 6, 7, and 8. The histone deacetylase inhibitor, sodium butyrate (250mg/kg, intraperitoneally), or saline was administered starting 2h prior to anesthesia or maternal separation and continued daily until the end of behavioral tests, which were performed between postnatal days 33 and 50. Upon completion of the behavioral tests, the brain tissues were harvested for further analysis. Rats neonatally exposed to sevoflurane exhibited decreased freezing time in the fear conditioning contextual test and increased escape latency, decreased time in target quadrant, and number of platform crossings in the Morris water maze test. The sevoflurane-exposed rats had lower hippocampal density of dendritic spines, reduced levels of the brain-derived neurotrophic factor, c-fos protein, microtubule-associated protein 2, synapsin1, postsynaptic density protein 95, pCREB/CREB, CREB binding protein, and acetylated histones H3 and H4, and increased levels of histone deacetylases 3 and 8. These neurobehavioral abnormalities were normalized in the sevoflurane-exposed rats treated with sodium butyrate. Our findings provide evidence that neonatal exposure to sevoflurane induces neurobehavioral abnormalities and long-lasting alterations in histone acetylation; normalization of histone acetylation may alleviate the neurodevelopmental side effects of the anesthetic.

Indexed as

AcetylationAnimalsBrain-Derived Neurotrophic FactorHippocampusHistonesMaternal DeprivationMethyl EthersMicrotubule-Associated ProteinsProto-Oncogene Proteins c-fosRats, Sprague-DawleySevofluraneTimeBrain-Derived Neurotrophic FactorHistonesMethyl EthersMicrotubule-Associated ProteinsProto-Oncogene Proteins c-fosSevofluraneHippocampusHistone acetylationMaternal separationNeonatal ratsSevofluraneSynaptic plasticity

Identifiers

PMID27001149
PMCPMC4860151
OpenAlexW2301018241

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.