Temporal Characterization of Microglia-Associated Pro- and Anti-Inflammatory Genes in a Neonatal Inflammation-Sensitized Hypoxic-Ischemic Brain Injury Model

被引:18
|
作者
Bernis, Maria E. [1 ,2 ]
Schleehuber, Yvonne [1 ,2 ]
Zweyer, Margit [1 ,2 ]
Maes, Elke [1 ,2 ]
Felderhoff-Mueser, Ursula [3 ]
Picard, Daniel [4 ,5 ]
Sabir, Hemmen [1 ,2 ,3 ]
机构
[1] Childrens Hosp Univ Bonn, Dept Neonatol & Pediat Intens Care, Bonn, Germany
[2] DZNE, Bonn, Germany
[3] Univ Duisburg Essen, Univ Hosp Essen, Dept Pediat Neonatol & Expt Perinatal Neurosci 1, Essen, Germany
[4] German Consortium Translat Canc Res DKTK, Div Pediat Neurooncogen, Partner Site Essen Dusseldorf, Dusseldorf, Germany
[5] Heinrich Heine Univ, Med Fac, Dept Pediat Oncol Hematol & Clin Immunol, Dusseldorf, Germany
关键词
BACTERIAL-ENDOTOXIN SENSITIZES; WHITE-MATTER; THERAPEUTIC HYPOTHERMIA; CEREBRAL-PALSY; ENCEPHALOPATHY; LIPOPOLYSACCHARIDE; CYTOKINES; TIME; TERM; INFANTS;
D O I
10.1155/2022/2479626
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Hypoxic-ischemic encephalopathy (HIE) mainly affects preterm and term newborns, leading to a high risk of brain damage. Coexisting infection/inflammation and birth asphyxia are key factors associated with intracerebral increase of proinflammatory cytokines linked to HIE. Microglia are key mediators of inflammation during perinatal brain injury, characterized by their phenotypic plasticity, which may facilitate their participation in both the progression and resolution of injury-induced inflammation. The purpose of this study was to investigate the temporal expression of genes associated with pro- and anti-inflammatory cytokines as well as the nucleotide-binding domain, leucine-rich repeat protein (NLRP-3) inflammasome from microglia cells. For this purpose, we used our established neonatal rat model of inflammation-sensitized hypoxic-ischemic (HI) brain injury in seven-day-old rats. We assessed gene expression profiles of 11 cytokines and for NLRP-3 using real-time PCR from sorted CD11b/c microglia of brain samples at different time points (3.5 h after LPS injection and 0, 5, 24, 48, and 72 hours post HI) following different treatments: vehicle, E. coli lipopolysaccharide (LPS), vehicle/HI, and LPS/HI. Our results showed that microglia are early key mediators of the inflammatory response and exacerbate the inflammatory response following HI, polarizing into a predominant proinflammatory M1 phenotype in the early hours post HI. The brains only exposed to HI showed a delay in the expression of proinflammatory cytokines. We also demonstrated that NLRP-3 plays a role in the inflammatory resolution with a high expression after HI insult. The combination of both, a preinfection/inflammation condition and hypoxia-ischemia, resulted in a higher proinflammatory cytokine storm, highlighting the significant contribution of acute inflammation sensitizing prior to a hypoxic insult on the severity of perinatal brain damage.
引用
收藏
页数:16
相关论文
共 21 条
  • [1] Early Pro-inflammatory Microglia Activation After Inflammation-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Rats
    Serdar, Meray
    Kempe, Karina
    Rizazad, Mandana
    Herz, Josephine
    Bendix, Ivo
    Felderhoff-Mueser, Ursula
    Sabir, Hemmen
    FRONTIERS IN CELLULAR NEUROSCIENCE, 2019, 13
  • [2] Acute Seizure Activity in Neonatal Inflammation-sensitized Hypoxic-ischemic Brain Injury
    June, Angelina S.
    Wagley, Pravin
    Kuan, Alex
    Burnsed, Jennifer
    PEDIATRICS, 2022, 149 (01)
  • [3] A Ferret Model of Inflammation-sensitized Late Preterm Hypoxic-ischemic Brain Injury
    Wood, Thomas
    Moralejo, Daniel
    Corry, Kylie
    Fisher, Cole
    Snyder, Jessica M.
    Acuna, Vivienne
    Holden-Hunt, Alair
    Virk, Simar
    White, Olivia
    Law, Janessa
    Parikh, Pratik
    Juul, Sandra E.
    JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2019, (153):
  • [4] Temporal Characterization of Microglia/Macrophage Phenotypes in a Mouse Model of Neonatal Hypoxic-Ischemic Brain Injury
    Erkenstam, Nina Hellstrom
    Smith, Peter L. P.
    Fleiss, Bobbi
    Nair, Syam
    Svedin, Pernilla
    Wang, Wei
    Bostrom, Martina
    Gressens, Pierre
    Hagberg, Henrik
    Brown, Kelly L.
    Savman, Karin
    Mallard, Carina
    FRONTIERS IN CELLULAR NEUROSCIENCE, 2016, 10
  • [5] Early neutrophil infiltration is critical for inflammation-sensitized hypoxic-ischemic brain injury in newborns
    Yao, Hui-Wen
    Kuan, Chia-Yi
    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2020, 40 (11): : 2188 - 2200
  • [6] Involvement of CXCL1/CXCR2 During Microglia Activation Following Inflammation-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Rats
    Serdar, Meray
    Kempe, Karina
    Herrmann, Ralf
    Picard, Daniel
    Remke, Marc
    Herz, Josephine
    Bendix, Ivo
    Felderhoff-Mueser, Ursula
    Sabir, Hemmen
    FRONTIERS IN NEUROLOGY, 2020, 11
  • [7] Early neutrophil depletion reduces inflammation-sensitized hypoxic-ischemic brain injury in mouse neonates.
    Yao, Hui-Wen
    Kuan, Chia-Yi
    JOURNAL OF IMMUNOLOGY, 2018, 200 (01):
  • [8] Blocking Lymphocyte Trafficking with FTY720 Prevents Inflammation-Sensitized Hypoxic-Ischemic Brain Injury in Newborns
    Yang, Dianer
    Sun, Yu-Yo
    Bhaumik, Siddhartha Kumar
    Li, Yikun
    Baumann, Jessica M.
    Lin, Xiaoyi
    Zhang, Yujin
    Lin, Shang-Hsuan
    Dunn, R. Scott
    Liu, Chia-Yang
    Shie, Feng-Shiun
    Lee, Yi-Hsuan
    Wills-Karp, Marsha
    Chougnet, Claire A.
    Kallapur, Suhas G.
    Lewkowich, Ian P.
    Lindquist, Diana M.
    Murali-Krishna, Kaja
    Kuan, Chia-Yi
    JOURNAL OF NEUROSCIENCE, 2014, 34 (49): : 16467 - 16481
  • [9] Knockdown of NF-κB-inducing kinase prevents inflammation-sensitized hypoxic-ischemic brain injury in newborns
    Ji, Qiaoyun
    Luo, Shan
    Li, Jingrong
    Wang, Hua
    Yang, Fan
    INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY, 2017, 10 (02): : 1558 - 1566
  • [10] Atorvastatin Promotes Pro/anti-inflammatory Phenotypic Transformation of Microglia via Wnt/β-catenin Pathway in Hypoxic-Ischemic Neonatal Rats
    Yu, Luting
    Huang, Lingyi
    Zhao, Yuanyuan
    Liu, Shixi
    Zhou, Ruixi
    Yue, Yan
    Sun, Hao
    Su, Xiaojuan
    Liu, Qian
    Li, Shiping
    Ying, Junjie
    Zhao, Fengyan
    Qu, Yi
    MOLECULAR NEUROBIOLOGY, 2024, 61 (06) : 3559 - 3577