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Anesthetic Isoflurane or Desflurane Plus Surgery Differently Affects Cognitive Function in Alzheimer’s Disease Transgenic Mice

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Abstract

Anesthesia/surgery could be associated with cognitive impairment and Alzheimer’s disease neuropathogenesis. However, whether surgery under different anesthetics has different effects on cognitive function remains largely unknown. We therefore set out to compare effects of anesthetic isoflurane or desflurane plus surgery on cognitive function and hippocampus levels of synaptic marker (postsynaptic density-95 and synaptophysin) and ATP. Five-month-old AD Transgenic (Tg) (FAD5X) and wild-type male mice received isoflurane or desflurane plus abdominal surgery. We assessed cognitive function in Barnes maze and measured hippocampus levels of postsynaptic density-95, synaptophysin, and ATP in the mice. We determined whether vitamin K2 could mitigate these anesthesia/surgery-induced changes. Isoflurane, but not desflurane, plus surgery increased escape latency and escape distance in Barnes maze probe test and reduced postsynaptic density-95, synaptophysin, and ATP levels as compared to control condition in AD Tg mice. Vitamin K2 attenuated the anesthesia/surgery-induced changes in the AD Tg mice. These findings suggest that isoflurane, but not desflurane, plus surgery might induce cognitive impairment via causing brain energy deficits. Pending confirmative studies in both animals and humans suggest desflurane could be a better choice for AD patients when surgery is needed. Moreover, vitamin K2 could treat cognitive deficiency associated with anesthesia and surgery.

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Acknowledgements

This research was supported by R01GM088801, R01AG041274, and R01HD 086977 from the National Institutes of Health, Bethesda, MD (to Z.X.). Dr. Edward Marcantonio was funded by the following grants from the National Institute on Aging: P01 AG031720, R01AG030618, K24AG035075, and R01AG051658. Dr. Greg Crosby was funded by the following grants from the National Institute on Aging: R21AG048637 and RO1AG051812. Dr. Yuan Shen was funded by 81571034 from the National Natural Science Foundation of China. The costs of isoflurane, desflurane, and EMLA cream (2.5% lidocaine and 2.5% prilocaine) were generously provided by the Department of Anesthesia, Critical Care and Pain Medicine at Massachusetts General Hospital. The studies were performed in the Geriatric Anesthesia Research Unit in the Department of Anesthesia, Critical Care and Pain Medicine at Massachusetts General Hospital, Boston, MA. These works should be attributed to the Department of Anesthesia, Critical Care and Pain Medicine at Massachusetts General Hospital and Harvard Medical School.

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Authors and Affiliations

  1. Department of Anesthesia, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China

    Huihui Miao

  2. Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 4310, Charlestown, MA, 02129-2060, USA

    Huihui Miao, Yuanlin Dong, Yiying Zhang & Zhongcong Xie

  3. Massachusetts General Hospital Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA

    Hui Zheng

  4. Department of Psychiatry, Tenth People’s Hospital of Tongji University, Shanghai, 200072, People’s Republic of China

    Yuan Shen

  5. Department of Anesthesia, Brigham & Women’s Hospital and Harvard Medical School, Boston, MA, 02115, USA

    Gregory Crosby & Deborah J. Culley

  6. Divisions of General Medicine and Primary Care and Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA

    Edward R. Marcantonio

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  1. Huihui Miao
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Contributions

Z.X., H.M., Y.Z., Y.S., G.C., D.J.C., and E.M. conceived and designed the project. H.M., Y.D., Y.Z., and H.Z. performed all the experiments, analyzed the data, and prepared the figures. Z.X. and H.M. wrote the manuscript. All authors reviewed the manuscript.

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Correspondence to Zhongcong Xie.

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Miao, H., Dong, Y., Zhang, Y. et al. Anesthetic Isoflurane or Desflurane Plus Surgery Differently Affects Cognitive Function in Alzheimer’s Disease Transgenic Mice. Mol Neurobiol 55, 5623–5638 (2018). https://doi.org/10.1007/s12035-017-0787-9

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