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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.
Brain Res. 2015 Oct 05; 1622:230-9.BR

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+Show Affiliations

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.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.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.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.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.Department of Nursing, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, PR China. Electronic address: tingtinghu91@hotmail.com.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.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26080076

Citation

Gao, Weiwei, et al. "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." Brain Research, vol. 1622, 2015, pp. 230-9.
Gao W, Zhao Z, Yu G, et al. 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. Brain Res. 2015;1622:230-9.
Gao, W., Zhao, Z., Yu, G., Zhou, Z., Zhou, Y., Hu, T., Jiang, R., & Zhang, J. (2015). 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. Brain Research, 1622, 230-9. https://doi.org/10.1016/j.brainres.2015.04.035
Gao W, et al. 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. Brain Res. 2015 Oct 5;1622:230-9. PubMed PMID: 26080076.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Gao,Weiwei, AU - Zhao,Zilong, AU - Yu,Gongjie, AU - Zhou,Ziwei, AU - Zhou,Yuan, AU - Hu,Tingting, AU - Jiang,Rongcai, AU - Zhang,Jianning, Y1 - 2015/06/12/ PY - 2015/02/22/received PY - 2015/04/14/revised PY - 2015/04/17/accepted PY - 2015/6/17/entrez PY - 2015/6/17/pubmed PY - 2016/6/2/medline KW - Blood brain barrier KW - Inflammatory cytokine KW - Nuclear factor-kappa B (NF-κB) KW - Traumatic brain injury SP - 230 EP - 9 JF - Brain research JO - Brain Res. VL - 1622 N2 - 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. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/26080076/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(15)00331-5 DB - PRIME DP - Unbound Medicine ER -