English  |  正體中文  |  简体中文  |  Items with full text/Total items : 17419/19718 (88%)
Visitors : 6177662      Online Users : 774
RC Version 7.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
  • Adv. Search
    HomeLoginUploadHelpAboutAdminister Goto mobile version
    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/30983

    標題: CXCL5 signaling is a shared pathway of neuroinflammation and blood-brain barrier injury contributing to white matter injury in the immature brain
    作者: Wang, Lin-Yu
    Tu, Yi-Fang
    Lin, Yung-Chieh
    Huang, Chao-Ching
    貢獻者: Chi Mei Med Ctr, Dept Pediat
    Chia Nan Univ Pharm & Sci, Dept Childhood Educ & Nursery
    Natl Cheng Kung Univ, Coll Med, Natl Cheng Kung Univ Hosp, Dept Pediat
    Natl Cheng Kung Univ, Coll Med, Inst Clin Med
    Taipei Med Univ, Coll Med, Dept Pediat
    Taipei Med Univ, Wan Fang Hosp, Dept Pediat
    關鍵字: CXCL5
    Blood-brain barrier
    Hypoxic ischemia
    White matter injury
    Immature brain
    Preterm infant
    日期: 2016-01
    上傳時間: 2018-01-18 11:39:12 (UTC+8)
    出版者: Biomed Central Ltd
    摘要: Background: In very preterm infants, white matter injury is a prominent brain injury, and hypoxic ischemia (HI) and infection are the two primary pathogenic factors of this injury. Microglia and microvascular endothelial cells closely interact; therefore, a common signaling pathway may cause neuroinflammation and blood-brain barrier (BBB) damage after injury to the immature brain. CXC chemokine ligand 5 (CXCL5) is produced in inflammatory and endothelial cells by various organs in response to insults. CXCL5 levels markedly increased in the amniotic cavity in response to intrauterine infection and preterm birth in clinical studies. The objective of this study is to determine whether CXCL5 signaling is a shared pathway of neuroinflammation and BBB injury that contributes to white matter injury in the immature brain. Methods: Postpartum day 2 (P2) rat pups received lipopolysaccharide (LPS) followed by 90-min HI. Immunohistochemical analyses were performed to determine microglial activation, neutrophil infiltration, BBB damage, and myelin basic protein and glial fibrillary acidic protein expression. Immunofluorescence experiments were performed to determine the cellular distribution of CXCL5. Pharmacological tests were performed to inhibit or enhance CXCL5 activity. Results: On P2, predominant increases in microglial activation and BBB damage were observed 24 h after LPS-sensitized HI induction, and white matter injury (decreased myelination and increased astrogliosis) was observed on P12 compared with controls. Immunohistochemical analyses revealed increased CXCL5 expression in the white matter 6 and 24 h after insult. Immunofluorescence experiments revealed upregulated CXCL5 expression in the activated microglia and endothelial cells 24 h after insult. CXCL5 inhibition by SB225002, a selective nonpeptide inhibitor of CXCR2, significantly attenuated microglial activation and BBB damage, increased myelination, and reduced astrogliosis in the white matter after LPS-sensitized HI. In addition, CXCL5-sensitized HI or CXCL5 alone significantly induced BBB damage and white matter injury in association with different neuroinflammation mechanisms. CXCL5-sensitized HI-induced microglial activation and neutrophil infiltration, whereas CXCL5 alone predominately caused neutrophil infiltration. Conclusions: CXCL5 is a potential biomarker for white matter injury in preterm infants. Pharmacological blockade of CXCL5 signaling that attenuates dysregulated neuroinflammation can be used a therapeutic strategy against white matter injury in the immature brain.
    關聯: Journal of Neuroinflammation, v.13:6
    Appears in Collections:[嬰幼兒保育系] 期刊論文

    Files in This Item:

    File Description SizeFormat
    30983.pdf4275KbAdobe PDF98View/Open

    All items in CNU IR are protected by copyright, with all rights reserved.

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback