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Ginsenoside Rg1 provides neuroprotection against blood brain barrier disruption and neurological injury in a rat model of cerebral ischemia/reperfusion through downregulation of aquaporin 4 expression
Institution:1. Department of Neurology, Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, Hebei, 050000, PR China;2. Hebei Key Laboratory of Vascular Homeostasis and Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, 215 Hepingxi Road, Shijiazhuang, Hebei, 050000, PR China;1. Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Medical College of Qingdao University, Qingdao, PR China;2. Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, People’s Republic of China;3. Department of Special Medicine, Medical College of Qingdao University, Qingdao, People’s Republic of China;4. Department of Physiology, Medical College of Taishan, Taian, People’s Republic of China;1. Department of Pharmacology, College of Basic Medicine, Kunming Medical University, Kunming, Yunnan, PR China;2. Department of Biochemistry, College of Basic Medicine, Kunming Medical University, Kunming, Yunnan, PR China;3. School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, Australia;4. Cardiovascular Division and Lillehei Heart Institute, University of Minnesota, MN, USA;5. Department of Cardiology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, PR China;1. Pediatric Emergency Critical Care Center, Children’s Hospital of Fudan University, Shanghai, PR China;2. Department of Medical Laboratory, Jining No.1 People’s Hospital, Jining, Shandong, PR China;3. Department of Neonatology, Shanghai Baijia Maternity Hospital, Shanghai, PR China;1. Neurobiology Laboratory, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad, 44000, Pakistan;2. Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA;3. Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Australia;4. Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran;5. Department of Chemistry, ICET, Federal University of Mato Grosso (UFMT), Av. Fernando Corrêa da Costa, 2367, CEP 78060-900, Cuiabá, MT, Brazil
Abstract:Ginsenoside Rg1 is regarded as one of main bioactive compounds responsible for pharmaceutical actions of ginseng with little toxicity and has been shown to have possibly neuroprotective effects. However, the mechanism of its neuroprotection for acute ischemic stroke is still elusive. The purpose of present study is thus to assess the neuroprotective effects of the ginsenoside Rg1 against blood brain barrier disruption and neurological injury in a rat model of cerebral ischemia/reperfusion, and then to explore the mechanisms for these neuroprotective effects by targeting aquaporin 4. Focal cerebral ischemia was induced by middle cerebral artery occlusion. Neurological examinations were performed by using Longa's 5-point scale. Evans blue dye was used to investigate the effects of ginsenoside Rg1 on blood brain barrier permeability. Immunohistochemical analysis and real-time fluorescence quantitative polymerase chain reaction were used to assess aquaporin 4 expression. As a result, general linear model with repeated measures analysis of variance for neurological scores at 5 repeated measures showed that ginsenoside Rg1-treated group could significantly reduce the changing trend of neurological deficit scores when compared with the middle cerebral artery occlusion model group (p < 0.05). Compared with the middle cerebral artery occlusion model group, ginsenoside Rg1 group has significantly decreased Evans blue content and reduced aquaporin 4 expression at each time point (p < 0.05). In conclusion, ginsenoside Rg1 as a ginsenoside neuroprotective agent could improve neurological injury, attenuate blood brain barrier disruption and downregulate aquaporin 4 expression induced by cerebral ischemia/reperfusion insults in rats.
Keywords:Stroke  Ginsenoside Rg1  Neuroprotection  Blood brain barrier disruption  Aquaporin 4
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