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