Adenosine A1 receptors contribute to immune regulation after neonatal hypoxic ischemic brain injury
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  • 作者:Max Winerdal ; Malin E. Winerdal ; Ying-Qing Wang…
  • 关键词:Brain hypoxic ; ischemia ; Neuroimmunomodulation ; Neonatology ; Adenosine A1 receptor ; Cellular immunity ; Statistical data interpretation
  • 刊名:Purinergic Signalling
  • 出版年:2016
  • 出版时间:March 2016
  • 年:2016
  • 卷:12
  • 期:1
  • 页码:89-101
  • 全文大小:2,228 KB
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  • 作者单位:Max Winerdal (1)
    Malin E. Winerdal (2)
    Ying-Qing Wang (3) (5)
    Bertil B. Fredholm (3)
    Ola Winqvist (2) (4)
    Ulrika Ådén (1) (4)

    1. Department of Women’s and Children’s Health, Karolinska Institutet, 17176, Stockholm, Sweden
    2. Department of Medicine, Karolinska Institutet, 17176, Stockholm, Sweden
    3. Department of Physiology and Pharmacology, Karolinska Institutet, 17176, Stockholm, Sweden
    5. Neonatal Research Unit Q2:07, Karolinska Universitetssjukhuset Solna, 17176, Stockholm, Sweden
    4. Division of Antitumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203, Shanghai, People’s Republic of China
  • 刊物类别:Biomedical and Life Sciences
  • 刊物主题:Biomedicine
    Biomedicine
    Pharmacology and Toxicology
    Human Physiology
    Neurosciences
    Cancer Research
  • 出版者:Springer Netherlands
  • ISSN:1573-9546
文摘
Neonatal brain hypoxic ischemia (HI) often results in long-term motor and cognitive impairments. Post-ischemic inflammation greatly effects outcome and adenosine receptor signaling modulates both HI and immune cell function. Here, we investigated the influence of adenosine A1 receptor deficiency (A1R−/−) on key immune cell populations in a neonatal brain HI model. Ten-day-old mice were subjected to HI. Functional outcome was assessed by open locomotion and beam walking test and infarction size evaluated. Flow cytometry was performed on brain-infiltrating cells, and semi-automated analysis of flow cytometric data was applied. A1R−/− mice displayed larger infarctions (+33 %, p < 0.05) and performed worse in beam walking tests (44 % more mistakes, p < 0.05) than wild-type (WT) mice. Myeloid cell activation after injury was enhanced in A1R−/− versus WT brains. Activated B lymphocytes expressing IL-10 infiltrated the brain after HI in WT, but were less activated and did not increase in relative frequency in A1R−/−. Also, A1R−/− B lymphocytes expressed less IL-10 than their WT counterparts, the A1R antagonist DPCPX decreased IL-10 expression whereas the A1R agonist CPA increased it. CD4+ T lymphocytes including FoxP3+ T regulatory cells, were unaffected by genotype, whereas CD8+ T lymphocyte responses were smaller in A1R−/− mice. Using PCA to characterize the immune profile, we could discriminate the A1R−/− and WT genotypes as well as sham operated from HI-subjected animals. We conclude that A1R signaling modulates IL-10 expression by immune cells, influences the activation of these cells in vivo, and affects outcome after HI. Keywords Brain hypoxic-ischemia Neuroimmunomodulation Neonatology Adenosine A1 receptor Cellular immunity Statistical data interpretation

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