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Neonatal Repeated Exposure to Isoflurane not Sevoflurane in Mice Reversibly Impaired Spatial Cognition at Juvenile-Age

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Abstract

Inhalation anesthetics facilitate surgical procedures in millions of children each year. However, animal studies demonstrate that exposure to the inhalation anesthetic isoflurane may cause neuronal cell death in developing brains. The long-term cytotoxic effects of sevoflurane, the most popular pediatric anesthetic, have not been compared with isoflurane. Thus, this study was designed to compare the effects of equipotent doses of these two anesthetics on neonatal long-term neurotoxicity. Postnatal 7-day-old (P7) C57/BL male mice were exposed to 1.5% isoflurane or 2.2% sevoflurane 2 h a day for 3 days. Non-anesthetized mice served as controls. The effects of anesthesia on learning and memory were assessed using the Morris Water Maze (MWM) at Postnatal days 30 (P30) and P60 respectively. The hippocampal content of N-methyl-d-aspartate receptor subunits (NMDA), brain-derived neurotrophic factor (BDNF), and synaptophysin (Syn) were determined by Western Blot. Neuron structure and apoptosis were assessed via Nissl and TUNEL staining, respectively. The isoflurane group exhibited cognitive impairment at P30. Repeated inhalation of isoflurane or sevoflurane caused different degrees of apoptosis and damaged hippocampal neurons in neonatal mice, particularly isoflurane. In neonatal mice, repeated exposure to isoflurane, but not sevoflurane, caused spatial cognitive impairments in juvenile mice. Our findings suggest that isoflurane induces significantly greater neurodegeneration than an equipotent minimum alveolar concentration of sevoflurane.

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Acknowledgements

This work was supported by the fundings: National Natural Science Foundation of China (81600934); Natural Science Foundation of Shanghai, China (16ZR1432200); Science Lead Supporting project of Shanghai, China (16411967700) awarded to Jianhui Liu.

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Authors and Affiliations

  1. Department of Anesthesiology, Tongji Hospital, Tongji University, Shanghai, 200065, China

    Jianhui Liu, Yanhong Zhao, Junjun Yang & Xiaoqing Zhang

  2. Department of Image and Radiology, Renji Hospital, Jiaotong University, Shanghai, 200127, China

    Wei Zhang

  3. Department of Image and Radiology, Tongji Hospital, Tongji University, Shanghai, 200065, China

    Peijun Wang

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  1. Jianhui Liu
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  2. Yanhong Zhao
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  3. Junjun Yang
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Correspondence to Jianhui Liu.

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Jianhui Liu and Yanhong Zhao are co-first authors.

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Liu, J., Zhao, Y., Yang, J. et al. Neonatal Repeated Exposure to Isoflurane not Sevoflurane in Mice Reversibly Impaired Spatial Cognition at Juvenile-Age. Neurochem Res 42, 595–605 (2017). https://doi.org/10.1007/s11064-016-2114-7

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