The impact of Ly6C low monocytes after cerebral hypoxia-ischemia in adult mice

Abstract

After an ischemic stroke, mononuclear phagocytic cells such as microglia, macrophages, and monocytes migrate to the lesion site and coordinate an immune response. Monocytes, which are recruited from the bloodstream after ischemic brain injury, can be categorized into two subsets in mice: inflammatory and patrolling monocytes. Although inflammatory monocytes (Ly6C hi) seem to have a protective role in stroke progression, the impact of patrolling monocytes (Ly6C low) is unknown. To address the role of Ly6C low monocytes in stroke, we generated bone marrow chimeric mice in which their hematopoietic system was replaced by Nr4a1 -/- cells, allowing the complete and permanent ablation of Ly6C low monocytes without affecting the Ly6C hi subset. We then subjected adult mice to cerebral hypoxia-ischemia using the Levine/Vannucci model. Functional outcomes after stroke such as body weight change, neurologic score, motor functions and spatial learning were not affected. Moreover, depletion in Ly6C low monocytes did not change significantly the total infarct size, cell loss, atrophy, the number, or the activation state of microglia/macrophages at the lesion site. These data suggest that Ly6C low patrolling monocytes are redundant in the progression and recovery of ischemic stroke. © 2014 ISCBFM.