Macrophage and monocyte subsets in response to ischemic stroke

Ischemic stroke is a leading cause of disability and mortality. Despite extensive efforts in stroke research, the only pharmacological treatment currently available is arterial recanalization, which has limited efficacy only in the acute phase of stroke. The neuroinflammatory response to stroke is believed to provide a wider time window than recanalization and has therefore been proposed as an attractive therapeutic target. In this review, we provide an overview of recent advances in the understanding of cellular and molecular responses of distinct macrophage populations following stroke, which may offer potential targets for therapeutic interventions. Specifically, we discuss the role of local responders in neuroinflammation, including the well-studied microglia as well as the emerging players, border-associated macrophages, and macrophages originating from the skull bone marrow. Additionally, we focus on the behavior of monocytes stemming from distant tissues such as the bone marrow and spleen. Finally, we highlight aging as a crucial factor modulating the immune response, which is often neglected in animal studies. Upon stroke, several subsets of macrophages, originating from different sources, localize differently within the lesion and are exposed to distinct environments. Consequently, these various subtypes exhibit diverse properties, which are influenced by the pathophysiological stage of ischemic stroke. Furthermore, the specific responses of these subtypes also depend on the age of the affected individuals.image