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Brain interstitial fluid drainage and extracellular space affected by inhalational isoflurane: in comparison with intravenous sedative dexmedetomidine and pentobarbital sodium

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Abstract

Brain interstitial fluid drainage and extracellular space are closely related to waste clearance from the brain. Different anesthetics may cause different changes of brain interstitial fluid drainage and extracellular space but these still remain unknown. Herein, effects of the inhalational isoflurane, intravenous sedative dexmedetomidine and pentobarbital sodium on deep brain matters’ interstitial fluid drainage and extracellular space and underlying mechanisms were investigated. When compared to intravenous anesthetic dexmedetomidine or pentobarbital sodium, inhalational isoflurane induced a restricted diffusion of extracellular space, a decreased extracellular space volume fraction, and an increased norepinephrine level in the caudate nucleus or thalamus with the slowdown of brain interstitial fluid drainage. A local administration of norepinephrine receptor antagonists, propranolol, atipamezole and prazosin into extracellular space increased diffusion of extracellular space and interstitial fluid drainage whilst norepinephrine decreased diffusion of extracellular space and interstitial fluid drainage. These findings suggested that restricted diffusion in brain extracellular space can cause slowdown of interstitial fluid drainage, which may contribute to the neurotoxicity following the waste accumulation in extracellular space under inhaled anesthesia per se.

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Acknowledgements

This work was supported by the National Major Scientific Research Instrument Development Project (61827808), the National Key Basic Research Program (973 Program, 2015CB856402), Beijing Brain Initiative of Beijing Municipal Science & Technology Commission (Z181100001518004), National Natural Science Foundation of China (81872051), and Peking University Clinical Scientist Program (BMU2019LCKXJ007). The authors also want to thank Prof. Jun Wang from the Department of Anesthesiology, Peking University Third Hospital and Prof. Zhiqian Tong from Beijing Institute for Brain Disorders, Capital Medical University as scientific advisors. We also thank Prof. Lan Yuan from the Peking University Health Science Center for technical support.

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Authors and Affiliations

  1. Department of Radiology, Peking University Third Hospital, Beijing, 100191, China

    Guomei Zhao, Hongbin Han, Yuanyuan Li & Yajuan Gao

  2. Beijing Key Laboratory of Magnetic Resonance Imaging Technology, Beijing, 100191, China

    Guomei Zhao, Hongbin Han, Jun Yang, Dehua Cui, Yuanyuan Li, Yajuan Gao & Jing Zou

  3. Institute of Medical Technology, Peking University, Beijing, 100191, China

    Hongbin Han

  4. Department of Neurosurgery, Peking University Third Hospital, Beijing, 100191, China

    Jun Yang

  5. Department of Cardiology, Peking University Shougang Hospital, Beijing, 100144, China

    Min Sun

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  1. Guomei Zhao
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Correspondence to Hongbin Han or Jun Yang.

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Zhao, G., Han, H., Yang, J. et al. Brain interstitial fluid drainage and extracellular space affected by inhalational isoflurane: in comparison with intravenous sedative dexmedetomidine and pentobarbital sodium. Sci. China Life Sci. 63, 1363–1379 (2020). https://doi.org/10.1007/s11427-019-1633-3

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