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Heightened stress response and cognitive impairment after repeated neonatal sevoflurane exposures might be linked to excessive GABAAR-mediated depolarization

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Abstract

Objective

Children with repeated exposures to anesthesia at an early age are at an increased risk of cognitive impairment. Data in the literature link increased developmental depolarizing γ-aminobutyric acid (GABA) type A receptor (GABAAR) at younger age to neurodevelopmental disorders. Here we investigated the involvement of GABAergic signaling during development in mediating the adverse effects of repeated sevoflurane exposures.

Methods

Sprague–Dawley male rats received repeated exposures to 3 % sevoflurane for 2 h daily for 3 consecutive days on postnatal days (P) 4, 5, and 6; maternally separated and unseparated rats served as controls. A subgroup of rats received three injections of the Na+–K+–2Cl− cotransporter inhibitor, bumetanide (1.82 mg/kg, intraperitoneally) 15 min prior to initiation of each sevoflurane exposure.

Results

The results showed that repeated neonatal sevoflurane exposures contribute to learning and memory impairment in the Morris water maze (MWM) at P60. The corticosterone level was significantly increased immediately after repeated neonatal sevoflurane exposures. Repeated neonatal sevoflurane exposures heightened the secretion of corticosterone in response to stress in P7 and P60 rats. Pretreatment of male rats prior to each sevoflurane exposure with bumetanide attenuated the corticosterone level immediately after repeated neonatal sevoflurane exposures, normalized endocrine response to stress at P7 and P60, and attenuated the sevoflurane-induced learning and memory impairment in the MWM.

Conclusion

These data suggested that the heightened stress response and cognitive impairment after repeated neonatal sevoflurane exposures might be linked to excessive GABAAR-mediated depolarization.

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Acknowledgments

This work was supported by grants from the Health Department of Jiangsu Province (No. 90014002) and Yancheng Health Department (No. 2015037).

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    Authors and Affiliations

    1. Department of Anesthesiology, The First People’s Hospital of Yancheng, Yancheng, 224005, Jiangsu, People’s Republic of China

      Guanghai Liu, Tiangui Zhu, Aihua Zhang, Feng Li, Weidong Qian & Bin Qian

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    1. Guanghai Liu
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    2. Tiangui Zhu
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    3. Aihua Zhang
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    4. Feng Li
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    5. Weidong Qian
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    6. Bin Qian
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    Correspondence to Bin Qian.

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    The authors report no conflicts of interest.

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    G. Liu and T. Zhu have contributed equally to this work.

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    Liu, G., Zhu, T., Zhang, A. et al. Heightened stress response and cognitive impairment after repeated neonatal sevoflurane exposures might be linked to excessive GABAAR-mediated depolarization. J Anesth 30, 834–841 (2016). https://doi.org/10.1007/s00540-016-2215-0

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    • DOI: https://doi.org/10.1007/s00540-016-2215-0

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