title: Pre-administration of curcumin prevents neonatal sevoflurane exposure-induced neurobehavioral abnormalities in mice.
abstract: Sevoflurane, a commonly used inhaled anesthetic, can induce neuronal apoptosis in the developing rodent brain and correlate with functional neurological impairment later in life. However, the mechanisms underlying these deleterious effects of sevoflurane remain unclear and no effective treatment is currently available. Herein, the authors investigated whether curcumin can prevent the sevoflurane anesthesia-induced cognitive impairment in mice. Six-day-old C57BL/6 mice were exposed to 3% sevoflurane 2h daily for 3 consecutive days and were treated with curcumin at the dose of 20 mg/kg or vehicle 30 min before the sevoflurane anesthesia from postnatal days 6 (P6) to P8. Cognitive functions were evaluated by open field, Morris water maze, and fear conditioning tests on P61, P63-69, and P77-78, respectively. In another separate experiment, mice were killed on day P8 or P78, and the brain tissues were harvested and then subjected to biochemistry studies. Our results showed that repeated neonatal sevoflurane exposure led to significant cognitive impairment later in life, which was associated with increased neuronal apoptosis, neuroinflammation, oxidative nitrosative stress, and decreased memory related proteins. By contrast, pre-administration of curcumin ameliorated early neuronal apoptosis, neuroinflammation, oxidative nitrosative stress, memory related proteins, and later cognitive dysfunction. In conclusion, our data suggested that curcumin pre-administration can prevent the sevoflurane exposure-induced cognitive impairment later in life, which may be partly attributed to its ability to attenuate the neural apoptosis, inflammation, and oxidative nitrosative stress in mouse brain.
authors.affiliation: Department of Anesthesiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Mu-Huo
authors.initials: MH
authors.lastname: Ji
authors.affiliation: Department of Anesthesiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Qiu
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou, China.
authors.forename: Jiao-Jiao
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Xiao-Ru
authors.initials: XR
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Si-Hai
authors.initials: SH
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou, China. Electronic address: weiyanlee@sina.com.
authors.forename: Wei-Yan
authors.initials: WY
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou, China. Electronic address: yjyangjj@126.com.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Yang
mesh_terms: D000367:Age Factors; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D001784:Blood Gas Analysis; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D003214:Conditioning, Classical / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry; D004334:Drug Administration Schedule; D005106:Exploratory Behavior / Q000187:drug effects; D005239:Fear / Q000187:drug effects; D018782:Maze Learning / Q000187:drug effects; D008738:Methyl Ethers / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011897:Random Allocation; D011930:Reaction Time / Q000187:drug effects; D000077149:Sevoflurane; D013997:Time Factors
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D018696:Neuroprotective Agents; D000077149:Sevoflurane; D003474:Curcumin
keywords: Cognition; Curcumin; Neurotoxicity; Sevoflurane