title: VEGI attenuates the inflammatory injury and disruption of blood-brain barrier partly by suppressing the TLR4/NF-κB signaling pathway in experimental traumatic brain injury.
abstract: Acute traumatic brain injury (TBI) tends to cause the over-activation of inflammatory response and disruption of blood brain barrier (BBB), associating with long-term cognitive and behavioral dysfunction. Vascular endothelial growth inhibitor (VEGI), as a suppressor in the angiogenesis specifically by inducing apoptosis in proliferating endothelial cells, has been applied to different diseases, especially the tumors. But rare study had been done in the field of brain injury. So in this study, we investigated the effects and mechanisms associated with VEGI-induced neuroprotection following CNS injury in mice TBI models. We demonstrated that the VEGI treatment reduced the contusion brain tissue loss, the permeation of inflammatory cells (MPO(+)) and the activation of microglia (Iba-1(+)). The treatment up-regulated the tight junction proteins (CLN5, ZO-1 and OCLN), which are vital importance for the integrity of the blood brain barrier (BBB), the B-cell lymphoma 2 (Bcl-2) cell survival factors, while down-regulated the expression of TLR4, NF-κB and inflammatory cytokines (IL-1β, TNF-α, iNOS). The treatment also decreased the expression of reactive astrocytes (GFAP(+)), as well as the VEGF, and lowered the permeability of Evens Blue (EB). These findings suggested that the VEGI-treatment could alleviate the post-traumatic excessive inflammatory response, and maintain the stability of blood vessels, remitting the secondary brain damage.
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, PR China; Tianjin Neurological Institute, 154 Anshan Road, Tianjin 300052, PR China; Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, 154 Anshan Road, Tianjin 300052, PR China. Electronic address: hongw1980@hotmail.com.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, PR China; Tianjin Neurological Institute, 154 Anshan Road, Tianjin 300052, PR China; Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, 154 Anshan Road, Tianjin 300052, PR China. Electronic address: ZilongZ@psbc.org.
authors.forename: Zilong
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, PR China; Tianjin Neurological Institute, 154 Anshan Road, Tianjin 300052, PR China; Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, 154 Anshan Road, Tianjin 300052, PR China. Electronic address: yugongjie@hotmail.com.
authors.forename: Gongjie
authors.initials: G
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, PR China; Tianjin Neurological Institute, 154 Anshan Road, Tianjin 300052, PR China; Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, 154 Anshan Road, Tianjin 300052, PR China. Electronic address: 1985zhouziwei@163.com.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, PR China; Tianjin Neurological Institute, 154 Anshan Road, Tianjin 300052, PR China; Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, 154 Anshan Road, Tianjin 300052, PR China. Electronic address: zy963000@126.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Nursing, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, PR China. Electronic address: tingtinghu91@hotmail.com.
authors.forename: Tingting
authors.initials: T
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, PR China; Tianjin Neurological Institute, 154 Anshan Road, Tianjin 300052, PR China; Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, 154 Anshan Road, Tianjin 300052, PR China. Electronic address: jianghope@gmail.com.
authors.forename: Rongcai
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, PR China; Tianjin Neurological Institute, 154 Anshan Road, Tianjin 300052, PR China; Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, 154 Anshan Road, Tianjin 300052, PR China. Electronic address: jianningzhang@hotmail.com.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D018696:Neuroprotective Agents; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D042461:Vascular Endothelial Growth Factor A
keywords: Blood brain barrier; Inflammatory cytokine; Nuclear factor-kappa B (NF-κB); Traumatic brain injury