Oxymatrine improves blood-brain barrier integrity after cerebral ischemia-reperfusion injury by downregulating CAV1 and MMP9 expression |
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| Institution: | 1. State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China;2. PLA Center of Disease Control and Prevention, Beijing 100071, China;1. Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China;2. Beijing Shijitan Hospital, Capital Medical University, Beijing, China;3. Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China;4. Tianjin General Surgery Institute, Tianjin, China;1. School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region;2. State Key Laboratory of Component-Based Chinese Medicine, Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China;3. Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China;4. Department of Ophthalmology, The University of Hong Kong, Hong Kong Special Administrative Region;1. Fuzong Clinical Medical College of Fujian Medical University, Fuzhou 350025, China;2. Department of Neurosurgery, Affiliated Hospital of Putian University, Putian 351100, China;3. Department of Neurosurgery, The 900th Hospital of Joint Logistic Support Force, Fujian Medical University Fuzong Clinical College, Fuzhou 350025, China;4. Department of Pathology, The 900th Hospital of Joint Logistic Support Force, Fujian Medical University Fuzong Clinical College, Fuzhou 350025, China;5. Laboratory of Basic Medicine, The 900th Hospital of Joint Logistic Support Force, Fujian Medical University Fuzong Clinical College, Fuzhou 350025, China;1. Department of Pharmacology, Fujian Medical University, Fuzhou, Fujian, China;2. Fujian Key Laboratory of Brain Aging and Neurodegenerative Diseases, Department of Human Anatomy and Embryology, Fujian Medical University, Fuzhou, Fujian, China |
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| Abstract: | BackgroundIschemic stroke (IS) is a major neurological condition associated with extremely high morbidity and mortality worldwide. Oxymatrine (OMT), a quinolizidine alkaloid extracted from the root of Sophora flavescens, has neuroprotective properties and protects against IS. However, whether its protective effect involves alterations in the integrity of the blood-brain barrier (BBB) is unknown.PurposeHere, we used in vivo and in vitro models of IS to evaluate the protective effects of OMT and to establish whether its effects are mediated via the modulation of the BBB function.MethodsWe assessed the effects of OMT by using neurological function scores, triphenyltetrazolium chloride staining, Nissl staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling.ResultsOMT significantly prevented cellular damage, improved neurological function, and reduced BBB permeability in a mouse model of cerebral ischemia-reperfusion. Additionally, OMT protected the function of the tight junctions of bEend.3 cells against the consequences of oxygen-glucose deprivation. Furthermore, intracranial lentivirus injection of short hairpin RNA targeting Cav1 decreased caveolin-1 expression and inhibited the neuroprotective effects of OMT.ConclusionsOMT attenuated ischemia-reperfusion injury-induced damage to the BBB, and this neuroprotective action was at least partially dependent on the expression levels of CAV1 and MMP9 proteins. Therefore, OMT may offer effective protection against BBB injury induced by ischemia-reperfusion episodes. |
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