IMR Press / JIN / Volume 20 / Issue 3 / DOI: 10.31083/j.jin2003065
Open Access Original Research
Prenatal sevoflurane exposure causes abnormal development of the entorhinal cortex in rat offspring
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1 Department of Anesthesiology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 510623 Guangzhou, Guangdong, China
2 Department of Anesthesiology, Guangdong Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine), 510120 Guangzhou, Guangdong, China
3 Department of Anesthesiology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, 201318 Shanghai, China
*Correspondence: (Xingrong Song)
J. Integr. Neurosci. 2021, 20(3), 613–622;
Submitted: 14 March 2021 | Revised: 26 March 2021 | Accepted: 12 May 2021 | Published: 30 September 2021
Copyright: © 2021 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license (

As a gamma-aminobutyric acid type A receptor agonist sevoflurane is a common general anesthetic used in anesthesia and affects the neural development in offspring. We hypothesized that sevoflurane could regulate interneurons via the neuregulin-1-epidermal growth factor receptor-4 (NRG1–ErbB4) pathway in the entorhinal cortex (ECT) of the middle pregnancy. Six female rats in middle pregnancy (14.5 days of pregnancy) were randomly and equally divided into sevoflurane (SeV) and control groups. The rats in the SeV group were exposed to 4% sevoflurane for 3 hours. The expression levels of NRG1 and ErbB4, parvalbumin (PV) and glutamic acid decarboxylase (GAD67), and N-methyl-D-aspartate receptor subunit 2A (NR2A) and subunit 2B (NR2B) in offspring were examined through immunohistochemistry. The pyramidal neurons in the ECT were examined via Golgi staining. The levels of NRG1 and ErbB4 were significantly decreased (P < 0.01) and the levels of PV and GAD67 (interneurons) were found to be decreased in the SeV group (P < 0.01). The level of NR2B was found to be increased while the level of NR2A being decreased in the SeV group (P < 0.01). The development of pyramidal neurons was abnormal in the SeV group (P < 0.05). Conclusively, prenatal sevoflurane exposure could lead to the disturbance of the interneurons by activating the NRG1–ErbB4 pathway and subsequently result in abnormal development of pyramidal neurons in middle pregnancy. Prenatal sevoflurane exposure in middle pregnancy could be potentially harmful to the neural development of rat offspring. This study may reveal a novel pathway in the influence mechanism of sevoflurane on rat offspring.

Middle pregnancy
Entorhinal cortex
Fig. 1.
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