Abstract WP319: Calvaria Hematopoiesis and Neuroinflammation: Insights From a Murine Stroke Model

Abstract

Introduction: The human skull has traditionally been perceived as a static protective structure guarding the brain and meninges. However, emerging data suggest there is a dynamic hematopoietic stem cell niche within the upper portion of the skull, or calvaria. This niche is important for sensing and contributing to central nervous system (CNS) inflammation. Murine models reveal dynamic neutrophil migration from the skull that infiltrates the ischemic brain, via the meninges, following stroke. Methods: To better understand the acute dynamics of the calvaria immune cell response to ischemic stroke, we investigated changes in hematopoiesis following a 60-minute transient middle cerebral artery occlusion (tMCAO) in young adult male C57Bl/6J mice. Bone marrow stem/progenitor cell proliferation and differentiation in the calvaria were measured at several time points during the first week of stroke utilizing flow cytometry. Results: We observed significant stress-induced myelopoiesis in the calvaria at 24-hours post-tMCAO, consistent with recent literature. An increasing trend for myeloid skewing in the ipsilateral (versus contralateral) calvaria was noted, suggesting unilateral activation. We also found a significant increase in Ly6C hi monocytes and Ly6G + neutrophils in the calvaria and ventral skull bone at 72-hours post-tMCAO. Conclusions: Our findings collectively suggest the calvaria plays an integral role in the acute inflammatory response to stroke. As the skull bone marrow contributes innate immune cells that both amplify inflammation and participate in debris clearance, future studies may help identify novel targets for interventions aimed at mitigating stroke-induced neuroinflammation.