Abstract
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.