Anesthetic Sevoflurane Causes Neurotoxicity Differently in Neonatal Naïve and Alzheimer Disease Transgenic Mice

Author:

Lu Yan1,Wu Xu2,Dong Yuanlin3,Xu Zhipeng4,Zhang Yiying5,Xie Zhongcong6

Affiliation:

1. Research fellow, Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, and Associate Professor, Key Laboratory of Health Ministry in Congenital Malformation, The Affiliated Shengjing Hospital of China Medical Uni

2. Research fellow, Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Genetics and Aging Research Unit, Mass- General Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Associate Professor, Department of Forensic Pathology, Faculty of Forensic Medicine, China Medical University, Shenyang, Peoples Republic o

3. Senior Research Technologist, Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School.

4. Research fellow, Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School.

5. Research fellow, Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Department of Anatomy and Neurobiology, Xuzhou Medical College, Xuzhou, People's Republic of China.

6. Associate Professor, Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, and Massachusetts General Hospital and Harvard Medical School.

Abstract

Background Recent studies have suggested that children undergoing surgery under anesthesia could be at an increased risk for the development of learning disabilities, but whether anesthetics contribute to this learning disability is unclear. Therefore, the authors set out to assess the effects of sevoflurane, the most commonly used inhalation anesthetic, on caspase activation, apoptosis, beta-amyloid protein levels, and neuroinflammation in the brain tissues of neonatal naïve and Alzheimer disease (AD) transgenic mice. Methods Six-day-old naïve and AD transgenic (B6.Cg-Tg[amyloid precursor protein swe, PSEN1dE9]85Dbo/J) mice were treated with sevoflurane. The mice were killed at the end of the anesthesia, and the brain tissues were harvested and then subjected to Western blot, immunocytochemistry, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction. Results Herein, the authors show for the first time that sevoflurane anesthesia induced caspase activation and apoptosis, altered amyloid precursor protein processing, and increased beta-amyloid protein levels in the brain tissues of neonatal mice. Furthermore, sevoflurane anesthesia led to a greater degree of neurotoxicity in the brain tissues of the AD transgenic mice when compared with naïve mice and increased tumor necrosis factor-alpha levels in the brain tissues of only the AD transgenic mice. Finally, inositol 1,4,5-trisphosphate receptor antagonist 2-aminoethoxydiphenyl borate attenuated sevoflurane-induced caspase-3 activation and beta-amyloid protein accumulation in vivo. Conclusion These results suggest that sevoflurane may induce neurotoxicity in neonatal mice. AD transgenic mice could be more vulnerable to such neurotoxicity. These findings should promote more studies to determine the potential neurotoxicity of anesthesia in animals and humans, especially in children.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Anesthesiology and Pain Medicine

Reference37 articles.

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