Brait VH, et al. - In this study with adult male mice on the C57BL/6 or BALB/c backgrounds, researchers explored the effect of CD69 (an immunomodulatory molecule induced during lymphocyte activation) in brain damage after an ischemic stroke. Wild-type mice and CD69^−/− mice, and CD69^+/+ and CD69^−/− lymphocyte-deficient Rag2^−/− mice, and generated chimeric mice were included in the study, and ischemia was induced by transient or permanent middle cerebral artery occlusion. They assessed infarct volume, neurological function, and CD69 expression, as well as platelet function, fibrin(ogen) deposition, and VWF (von Willebrand factor) expression in brain vessels and VWF content and activity in plasma. They also carried out the tail-vein bleeding test. Compared with the wild-type mice, larger infarct volumes and worse neurological deficits were detected in CD69−/− mice following ischemia. Lymphocytes or other hematopoietic cells were not considered responsible for this worsening impact. Characterized by increased VWF and worse brain damage following ischemic stroke, a prothrombotic phenotype was promoted by CD69 deficiency. CD69 was thought to be acting as a downregulator of endothelial activation.