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      Cistanches alleviates sevoflurane‐induced cognitive dysfunction by regulating PPAR‐γ‐dependent antioxidant and anti‐inflammatory in rats

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          Abstract

          This study aimed to investigate the protective effects and underlying mechanisms of cistanche on sevoflurane‐induced aged cognitive dysfunction rat model. Aged (24 months) male SD rats were randomly assigned to four groups: control group, sevoflurane group, control + cistanche and sevoflurane + cistanche group. Subsequently, inflammatory cytokine levels were measured by ELISA, and the cognitive dysfunction of rats was evaluated by water maze test, open‐field test and the fear conditioning test. Three days following anaesthesia, the rats were killed and hippocampus was harvested for the analysis of relative biomolecules. The oxidative stress level was indicated as nitrite and MDA concentration, along with the SOD and CAT activity. Finally, PPAR‐γ antagonist was used to explore the mechanism of cistanche in vivo. The results showed that after inhaling the sevoflurane, 24‐ but not 3‐month‐old male SD rats developed obvious cognitive impairments in the behaviour test 3 days after anaesthesia. Intraperitoneal injection of cistanche at the dose of 50 mg/kg for 3 consecutive days before anaesthesia alleviated the sevoflurane‐induced elevation of neuroinflammation levels and significantly attenuated the hippocampus‐dependent memory impairments in 24‐month‐old rats. Cistanche also reduced the oxidative stress by decreasing nitrite and MDA while increasing the SOD and CAT activity. Moreover, such treatment also inhibited the activation of microglia. In addition, we demonstrated that PPAR‐γ inhibition conversely alleviated cistanche‐induced protective effect. Taken together, we demonstrated that cistanche can exert antioxidant, anti‐inflammatory, anti‐apoptosis and anti‐activation of microglia effects on the development of sevoflurane‐induced cognitive dysfunction by activating PPAR‐γ signalling.

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          Most cited references45

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          Post-Operative Cognitive Dysfunction: An exploration of the inflammatory hypothesis and novel therapies.

          Post-Operative Cognitive Dysfunction (POCD) is a highly prevalent condition with significant clinical, social and financial impacts for patients and their communities. The underlying pathophysiology is becoming increasingly understood, with the role of neuroinflammation and oxidative stress secondary to surgery and anaesthesia strongly implicated. This review aims to describe the putative mechanisms by which surgery-induced inflammation produces cognitive sequelae, with a focus on identifying potential novel therapies based upon their ability to modify these pathways.
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            Roles of Peroxisome Proliferator-Activated Receptor Gamma on Brain and Peripheral Inflammation

            Peroxisome proliferator-activated receptor gamma (PPARγ) has been implicated in the pathology of numerous diseases involving diabetes, stroke, cancer, or obesity. It is expressed in diverse cell types, including vessels, immune and glial cells, and neurons. PPARγ plays crucial roles in the regulation of cellular differentiation, lipid metabolism, or glucose homeostasis. PPARγ ligands also exert effects on attenuating degenerative processes in the brain, as well as in peripheral systems, and it has been associated with the control of anti-inflammatory mechanisms, oxidative stress, neuronal death, neurogenesis, differentiation, and angiogenesis. This review will highlight key advances in the understanding of the PPARγ-related mechanisms responsible for neuroprotection after brain injuries, both ischemia and traumatic brain injury, and it will also cover the natural and synthetic agonist for PPARγ, angiotensin receptor blockers, and PPARγ antagonists, used in experimental and clinical research. A better understanding of the pleiotropic mechanisms and applications of these drugs to improve the recovery and to repair the acute and chronic induced neuroinflammation after brain injuries will pave the way for more effective therapeutic strategies after brain deficits.
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              Oxidative stress and the pathogenesis of neurodegenerative disorders.

              Microglia-derived inflammatory neurotoxins play a principal role in the pathogenesis of neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and HIV-associated dementia; chief among these is reactive oxygen species. The detrimental effects of oxidative stress in the brain and nervous system are primarily a result of the diminished capacity of the central nervous system to prevent ongoing oxidative damage. A spectrum of environmental cues, mitochondrial dysfunction, accumulation of aberrant misfolded proteins, inflammation, and defects in protein clearance are known to evolve and form as a result of disease progression. These factors likely affect glial function serving to accelerate the tempo of disease. Understanding the relationships between disease progression, free radical formation, neuroinflammation, and neurotoxicity is critical to elucidating disease mechanisms and the development of therapeutic modalities to combat disease processes. In an era where populations continue to age, the prevalence and incidence of age-related neurodegenerative diseases are on the rise; therefore, the need for novel therapeutic strategies that attenuate neuroinflammation and protect neurons against oxidative stress is ever more immediate.
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                Author and article information

                Contributors
                ps7707@163.com
                Journal
                J Cell Mol Med
                J. Cell. Mol. Med
                10.1111/(ISSN)1582-4934
                JCMM
                Journal of Cellular and Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                1582-1838
                1582-4934
                04 December 2019
                January 2020
                : 24
                : 2 ( doiID: 10.1111/jcmm.v24.2 )
                : 1345-1359
                Affiliations
                [ 1 ] Department of Anesthesiology Seventh People’s Hospital of Shanghai University of TCM Shanghai China
                [ 2 ] Department of Anesthesiology Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Red Cross Cancer Center Nanjing Jiangsu China
                [ 3 ] Department of Pathology Seventh People’s Hospital of Shanghai University of TCM Shanghai China
                [ 4 ] Department of Neurology Seventh People’s Hospital of Shanghai University of TCM Shanghai China
                Author notes
                [*] [* ] Correspondence

                Yixin Zhou, Department of Neurology, Seventh People’s Hospital of Shanghai University of TCM, No. 358 Datong Road, Shanghai 200137, China.

                Email: ps7707@ 123456163.com

                Author information
                https://orcid.org/0000-0002-7565-0329
                Article
                JCMM14807
                10.1111/jcmm.14807
                6991648
                31802591
                f8fb0c3f-0a27-4834-9930-1d2304c195a4
                © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 February 2019
                : 06 September 2019
                : 29 September 2019
                Page count
                Figures: 8, Tables: 0, Pages: 15, Words: 8224
                Funding
                Funded by: Important Weak Subject Construction Project of Pudong Health and Family Planning Commission of Shanghai
                Award ID: PWZbr2017‐19
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                January 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.5 mode:remove_FC converted:30.01.2020

                Molecular medicine
                cistanche,postoperative cognitive dysfunction (pocd),ppar‐γ,sevoflurane
                Molecular medicine
                cistanche, postoperative cognitive dysfunction (pocd), ppar‐γ, sevoflurane

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