title: MiR-21 alleviates secondary blood-brain barrier damage after traumatic brain injury in rats.
abstract: Our recent studies have identified increased expression of miR-21 in brain following traumatic brain injury (TBI), which alleviated brain edema that related to the blood-brain barrier (BBB) leakage. To analyze the potential effect of miR-21 on secondary BBB damage after TBI, we employed the fluid percussion injury rat model and manipulated the expression level of miR-21 in brain. We found that miR-21 level in brain microvascular endothelial cells (BMVECs) in lesioned cerebral cortex can be upregulated or downregulated by intracerebroventricular infusion of miR-21 agomir or antagomir. Upregulated miR-21 level conferred a better neurological outcome of TBI, and alleviated TBI-induced secondary BBB damage and loss of tight junction proteins. To explore the molecular mechanism underlying this protective effect, we detected the impact of miR-21 on the expression of Angiopoietin-1(Ang-1) and Tie-2, which can promote the expression of tight junction proteins and amplify BBB stabilization. We found that miR-21 exerts the protective effect on BBB by activating the Ang-1/Tie-2 axis in BMVECs. Thus, miR-21 could be a potential therapeutic target for interventions of secondary BBB damage after TBI.
authors.affiliation: Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, China; Laboratory of Neuro-Trauma, Tianjin Neurological Institute, Tianjin 300052, China; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Xintong
authors.initials: X
authors.lastname: Ge
authors.affiliation: Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, China; Laboratory of Neuro-Trauma, Tianjin Neurological Institute, Tianjin 300052, China; Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, China; Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin 300052, China.
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Han
authors.affiliation: Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, China; Laboratory of Neuro-Trauma, Tianjin Neurological Institute, Tianjin 300052, China.
authors.forename: Fanglian
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Neurology, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Haichen
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, China; Laboratory of Neuro-Trauma, Tianjin Neurological Institute, Tianjin 300052, China; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Baoliang
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, China; Laboratory of Neuro-Trauma, Tianjin Neurological Institute, Tianjin 300052, China; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Rongcai
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, China; Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin 300052, China. Electronic address: leiping1974@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Lei
authors.affiliation: Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, China; Laboratory of Neuro-Trauma, Tianjin Neurological Institute, Tianjin 300052, China; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: jianningzhang@hotmail.com.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002199:Capillary Permeability / Q000502:physiology; D062507:Claudin-5 / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D055806:Microvessels / Q000378:metabolism* / Q000473:pathology; D062793:Occludin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley
chemical_list: D042683:Angiopoietin-1; D062507:Claudin-5; C491510:Cldn5 protein, rat; D035683:MicroRNAs; D062793:Occludin; C568987:Ocln protein, rat; D012333:RNA, Messenger; C546082:mirn21 microRNA, rat
keywords: Blood–brain barrier; Gene therapy; Secondary brain damage; Traumatic brain injury; miR-21