title: Dexmedetomidine improves early postoperative cognitive dysfunction in aged mice.
abstract: Postoperative cognitive dysfunction (POCD) is a frequent complication following major surgery in the elderly. However, the exact pathogenic mechanisms are still unknown. Dexmedetomidine, a selective alpha 2 adrenal receptor agonist, was revealed anesthesia and brain protective role. The present study aimed to examine whether dexmedetomdine protects against POCD induced by major surgical trauma under general anesthesia in aged mice. In the present study, cognitive function was assessed by Y-maze. Proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α), apoptosis-related factor caspase-3 and Bax were detected by real-time PCR, Western blot or immunohistochemistry. The results showed that anesthesia alone caused weak cognitive dysfunction on the first day after general anesthesia. Cognitive function in mice with splenectomy under general anesthesia was significantly exacerbated at the first and third days after surgery, and was significantly improved by dexmedetomidine administration. Splenectomy increased the expression of IL-1β, TNF-α, Bax and caspase-3 in hippocampus. These changes were significantly inversed by dexmedetomidine. These results suggest that hippocampal inflammatory response and neuronal apoptosis may contribute to POCD, and selective alpha 2 adrenal receptor excitation play a protective role.
authors.affiliation: Henan Key Laboratory for Pharmacology of Liver Diseases, Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou 450052, China; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, China; The Third People Hospital of Henan Province, 98 Funiu Road, Zhengzhou 450052, China.
authors.forename: Xiao-Lan
authors.initials: XL
authors.lastname: Qian
authors.affiliation: The First Affiliated Hospital, Zhengzhou University, 1 Jianshe East Road, Zhengzhou 450052, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Fuwai Hospital, National Center for cardiovascular Diseases, 167 Nouth Lishi Road, Beijing 100037, China.
authors.forename: Ming-Zheng
authors.initials: MZ
authors.lastname: Liu
authors.affiliation: The First Affiliated Hospital, Zhengzhou University, 1 Jianshe East Road, Zhengzhou 450052, China.
authors.forename: Yu-Bing
authors.initials: YB
authors.lastname: Zhou
authors.affiliation: Henan Key Laboratory for Pharmacology of Liver Diseases, Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou 450052, China; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, China.
authors.forename: Jing-Min
authors.initials: JM
authors.lastname: Zhang
authors.affiliation: Henan Key Laboratory for Pharmacology of Liver Diseases, Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou 450052, China; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, China.
authors.forename: Li
authors.initials: L
authors.lastname: Han
authors.affiliation: Henan Key Laboratory for Pharmacology of Liver Diseases, Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou 450052, China; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, China.
authors.forename: You-Mei
authors.initials: YM
authors.lastname: Peng
authors.affiliation: Henan Key Laboratory for Pharmacology of Liver Diseases, Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou 450052, China.
authors.forename: Jin-hua
authors.initials: JH
authors.lastname: Jiang
authors.affiliation: Henan Key Laboratory for Pharmacology of Liver Diseases, Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou 450052, China. Electronic address: wangqd@zzu.edu.cn.
authors.forename: Qing-Duan
authors.initials: QD
authors.lastname: Wang
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000375:Aging; D018681:Anesthetics, General / Q000009:adverse effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011183:Postoperative Complications / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011897:Random Allocation; D013156:Splenectomy / Q000009:adverse effects
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D018681:Anesthetics, General; D051017:Apoptosis Regulatory Proteins; D018836:Inflammation Mediators; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D020927:Dexmedetomidine
keywords: Aged; Anesthesia; Apoptosis; Dexmedetomidine; Inflammation; Postoperative cognitive dysfunction