Fingerprint of Circulating Immunocytes as Biomarkers for the Prognosis of Brain Inflammation and Neuronal Injury after Cardiac Arrest.

Fingerprint of Circulating Immunocytes as Biomarkers for the Prognosis of Brain Inflammation and Neuronal Injury after Cardiac Arrest.
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DOI:
10.1021/acschemneuro.3c00397
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发表时间:
2023-12-06
影响因子:
5
通讯作者:
Xu, Yan
Xu, Yan
中科院分区:
医学3区
文献类型:
--
作者:
Dou, Huanyu;Brandon, Nicole R.;Koper, Kerryann E.;Xu, Yan

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心脏骤停是世界上最危险的健康问题之一。结果预后很大程度上取决于神经学评估确定的大脑表现类别。目前很少有系统测试可用于预测出院生存率。在这里,我们展示了小鼠心脏骤停和复苏 (CAR) 的临床前研究结果,以识别循环免疫细胞的特征作为血液来源的生物标志物,以预测 CAR 后的结果。分别设计了循环血淋巴细胞和骨髓源性细胞的两个流式细胞术组,以与双侧海马选择性脆弱区域的神经炎症以及神经元和树突损失相关。我们发现,CD4+CD25+调节性T细胞、CD11b+CD11c–和CD11b+Ly6C+Ly6G+骨髓源性细胞,以及血液中共刺激分子CD80和CD86阳性的细胞与小胶质细胞的激活和星形细胞增多相关,CD4+CD25+T细胞还与神经元和树突状细胞的丢失相关。血液 T 细胞和单核细胞的指纹模式被设计为预测 CAR 结果的诊断工具。旨在识别心脏骤停患者的这些免疫细胞模式的血液测试将指导未来的临床试验,以建立更好的预测工具,以避免不必要的早期退出维持生命的治疗。
Cardiac arrest is one of the most dangerous health problems in the world. Outcome prognosis is largely based on cerebral performance categories determined by neurological evaluations. Few systemic tests are currently available to predict survival to hospital discharge. Here, we present the results from the preclinical studies of cardiac arrest and resuscitation (CAR) in mice to identify signatures of circulating immune cells as blood-derived biomarkers to predict outcomes after CAR. Two flow cytometry panels for circulating blood lymphocytes and myeloid-derived cells, respectively, were designed to correlate with neuroinflammation and neuronal and dendritic losses in the selectively vulnerable regions of bilateral hippocampi. We found that CD4+CD25+ regulatory T cells, CD11b+CD11c– and CD11b+Ly6C+Ly6G+ myeloid-derived cells, and cells positive for the costimulatory molecules CD80 and CD86 in the blood were correlated with activation of microglia and astrocytosis, and CD4+CD25+ T cells are additionally correlated with neuronal and dendritic losses. A fingerprint pattern of blood T cells and monocytes is devised as a diagnostic tool to predict CAR outcomes. Blood tests aimed at identifying these immunocyte patterns in cardiac arrest patients will guide future clinical trials to establish better prognostication tools to avoid unnecessary early withdrawal from life-sustaining treatment.
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