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 107 条
  • [91] Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances
    Volpe, Joseph J.
    [J]. LANCET NEUROLOGY, 2009, 8 (01) : 110 - 124
  • [92] Inhibition of Microglial TGFβ Signaling Increases Expression of Mrc1
    von Ehr, Alexander
    Attaai, Abdelraheim
    Neidert, Nicolas
    Potru, Phani Sankar
    Russ, Tamara
    Zoeller, Tanja
    Spittau, Bjoern
    [J]. FRONTIERS IN CELLULAR NEUROSCIENCE, 2020, 14
  • [93] CCL11 promotes migration and proliferation of mouse neural progenitor cells
    Wang, Feifei
    Baba, Nobuyasu
    Shen, Yuan
    Yamashita, Tatsuyuki
    Tsuru, Emi
    Tsuda, Masayuki
    Maeda, Nagamasa
    Sagara, Yusuke
    [J]. STEM CELL RESEARCH & THERAPY, 2017, 8 : 1 - 11
  • [94] Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
    Wang, Haidong
    Liddell, Chelsea A.
    Coates, Matthew M.
    Mooney, Meghan D.
    Levitz, Carly E.
    Schumacher, Austin E.
    Apfel, Henry
    Iannarone, Marissa
    Phillips, Bryan
    Lofgren, Katherine T.
    Sandar, Logan
    Dorrington, Rob E.
    Rakovac, Ivo
    Jacobs, Troy A.
    Liang, Xiaofeng
    Zhou, Maigeng
    Zhu, Jun
    Yang, Gonghuan
    Wang, Yanping
    Liu, Shiwei
    Li, Yichong
    Ozgoren, Ayse Abbasoglu
    Abera, Semaw Ferede
    Abubakar, Ibrahim
    Achoki, Tom
    Adelekan, Ademola
    Ademi, Zanfina
    Alemu, Zewdie Aderaw
    Allen, Peter J.
    AlMazroa, Mohammad AbdulAziz
    Alvarez, Elena
    Amankwaa, Adansi A.
    Amare, Azmeraw T.
    Ammar, Walid
    Anwari, Palwasha
    Cunningham, Solveig Argeseanu
    Asad, Majed Masoud
    Assadi, Reza
    Banerjee, Amitava
    Basu, Sanjay
    Bedi, Neeraj
    Bekele, Tolesa
    Bell, Michelle L.
    Bhutta, Zulfi Qar
    Blore, Jed D.
    Basara, Berrak Bora
    Boufous, Soufiane
    Breitborde, Nicholas
    Bruce, Nigel G.
    Linh Ngoc Bui
    [J]. LANCET, 2014, 384 (9947) : 957 - 979
  • [95] Treatment temperature and insult severity influence the neuroprotective effects of therapeutic hypothermia
    Wood, Thomas
    Osredkar, Damjan
    Puchades, Maja
    Maes, Elke
    Falck, Mari
    Flatebo, Torun
    Walloe, Lars
    Sabir, Hemmen
    Thoresen, Marianne
    [J]. SCIENTIFIC REPORTS, 2016, 6
  • [96] Chorioamnionitis and cerebral palsy in term and near-term infants
    Wu, YW
    Escobar, GJ
    Grether, JK
    Croen, LA
    Greene, JD
    Newman, TB
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2003, 290 (20): : 2677 - 2684
  • [97] Neuroinflammation in the central nervous system: Symphony of glial cells
    Yang, Qiao-qiao
    Zhou, Jia-wei
    [J]. GLIA, 2019, 67 (06) : 1017 - 1035
  • [98] Hypoxia-inducible factor-1 alpha is involved in RIP-induced necroptosis caused by in vitro and in vivo ischemic brain injury
    Yang, Xiao-Sa
    Yi, Tai-Long
    Zhang, Sai
    Xu, Zhong-Wei
    Yu, Ze-Qi
    Sun, Hong-Tao
    Yang, Cheng
    Tu, Yue
    Cheng, Shi-Xiang
    [J]. SCIENTIFIC REPORTS, 2017, 7
  • [99] Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors
    Yang, Yang
    Wang, Huanan
    Kouadir, Mohammed
    Song, Houhui
    Shi, Fushan
    [J]. CELL DEATH & DISEASE, 2019, 10 (2)
  • [100] Early neutrophil infiltration is critical for inflammation-sensitized hypoxic-ischemic brain injury in newborns
    Yao, Hui-Wen
    Kuan, Chia-Yi
    [J]. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2020, 40 (11) : 2188 - 2200