Quantitative and Correlational Analysis of Brain and Spleen Immune Cellular Responses Following Cerebral Ischemia

Stroke is a multiphasic process, and the initial ischemic phase of neuronal damage is followed by secondary innate and adaptive responses that unfold over days after stroke, offer a longer time frame of intervention, and represent a novel therapeutic target. Therefore, revealing the distinct functions of immune cells in both brain and periphery is important for identification of immunotherapeutic targets for stroke to extend the treatment time window. In this paper an examination of the cellular dynamics of the immune response in the central nervous system (CNS) and periphery provoked by cerebral ischemia is provided. New data is presented for the number of immune cells in brain and spleen of mice during the 7 days following middle cerebral artery occlusion (MCAO). A novel analysis of the correlation among various cell types in the brain and spleen following stroke is presented. It is found that the infiltrated macrophages in the ischemic hemisphere positively correlate with neutrophils which implies their synergic effect in migrating into the brain after stroke onset. It is noted that during infiltration of adaptive immune cells, the number of neutrophils correlate positively with T cells, which suggests neutrophils contribute to T cell infiltration in the stroked brain. Furthermore, the correlation among neurological deficit and various immune cells suggests that microglia and splenic adaptive immune cells (T and B cells) are protective while infiltrating peripheral myeloid cells (macrophage and neutrophils) worsen stroke outcome. Comprehension of such immune responses post cerebral ischemia is crucial for differentiating the drivers of outcomes and also predicting the stroke outcome.

Automated summary

The article investigates the cellular dynamics of immune responses in the central nervous system and periphery post stroke, highlighting correlations between different cell types in the brain and spleen following stroke. Findings suggest a synergistic effect between infiltrated macrophages and neutrophils in the ischemic hemisphere, as well as a positive correlation between neutrophils and T cells. Furthermore, the correlation between neurological deficits and immune cells indicates that microglia and splenic adaptive immune cells are protective, while infiltrating peripheral myeloid cells exacerbate stroke outcomes. Understanding these immune responses is crucial for predicting stroke outcomes and identifying therapeutic targets.