Previous studies investigating innate leukocyte recruitment into the brain after cerebral ischemia have shown conflicting results. Using distinct cell surface and intracellular markers, the current study evaluated the contributions of innate immune cells to the poststroke brain following 1-h middle cerebral artery occlusion (tMCAO) or permanent MCAO (pMCAO), and assessed whether these cells ascribed to an inflammatory state. Moreover, we examined whether there is evidence for leukocyte infiltration into the contralateral (CL) hemisphere despite the absence of stroke infarct. We observed the recruitment of peripheral neutrophils, monocytes and macrophages into the hemisphere ipsilateral (IL) to the ischemic brain infarct at 24 and 96 h following both tMCAO and pMCAO. In addition, we found evidence of increased leukocyte recruitment to the CL hemisphere but to a lesser extent than the IL hemisphere after stroke. Robust production of intracellular cytokines in the innate immune cell types examined was most evident at 24 h after pMCAO. Specifically, brain-associated neutrophils, monocytes and macrophages demonstrated stroke-induced production of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β, while only monocytes and macrophages exhibit a significant expression of arginase 1 (Arg1) after stroke. At 96 h after stroke, brain-resident microglia demonstrated production of TNF-α and IL-1β following both tMCAO and pMCAO. At this later timepoint, neutrophils displayed TNF-α production and brain-associated macrophages exhibited elevation of IL-1β and Arg1 after tMCAO. Further, pMCAO induced significant expression of Arg1 and IL-1β in monocytes and macrophages at 96 h, respectively. These results revealed that brain-associated innate immune cells display various stroke-induced inflammatory states that are dependent on the experimental stroke setting.
Keywords: heterogeneity; ischemia; neuroinflammation; neutrophils; stroke.
© 2022 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.