Role of bone marrow-derived macrophages (BMDMs) in neurovascular interactions during stroke

Abstract

Stroke is a leading cause of disability worldwide and hence remains a major medical concern. Besides several pathological features, such as excitotoxicity, peri-infarct depolarization, acidosis, reactive oxygen species generation, apoptosis, and necrosis, dysregulation of the immune system severely affects stroke outcomes. After stroke onset, microglia - the brain-resident macrophage immune cells - and peripheral immune cells affect stoke injury/recovery by releasing pro-inflammatory and/or anti-inflammatory cytokines depending on their microenvironment. These pro- or anti-inflammatory cytokines further affect integrity of the blood brain barrier (BBB) and modulate immune infiltration after stroke. Among peripheral immune cells, bone marrow-derived macrophages (BMDMs) play a critical role in stroke pathology which peaks between three and seven days post-stroke. BMDMs have been extensively studied for their role in exacerbation of stroke injury, however they have rarely been studied for their role in tissue repair. Nonetheless, these reparative roles are gaining attention since recent studies have shown either failure or worsening of long-term post-stroke recovery after blockade of peripheral immune infiltration. These diverse but paradoxical effects of infiltrating monocytes/macrophages encouraged us to summarize the latest findings in neuro-immune and immune-vascular interactions. This review highlights the multifaceted role of BMDMs in stroke onset and resolution, and emphasizes the significance of tapping the potential of these cells to gain better insight into disease progression and therapy.