Glia–immune interactions post-ischemic stroke and potential therapies

Although the primary responsibility of the immune system has for over a century been perceived as the protector of the host against infection in the peripheral organs, we now know the immune system also plays a vital role in recovery pathways associated with central nervous system (CNS) injury. There is mounting evidence that the blood–brain barrier does not preclude the CNS from immune surveillance. Of particular interest for this review is how microglia and astrocytes interact with the cells of the immune system to modulate repair and recovery mechanisms in ischemic stroke. Our review argues that by deepening our understanding of neuroimmunity, specifically the bidirectional glial–immune cell communications, a plethora of new therapeutic targets and mechanisms may be revealed. Consequently, this review instigates novel experimental approaches to neuroimmunology and fosters a more rapid discovery process for the treatment of stroke. Impact statement This article reviews glial cell interactions with the immune system post-ischemic stroke. Research has shown that glial cells in the brain play a role in altering phenotypes of other glial cells and have downstream immune cell targets ultimately regulating a neuroinflammatory response. These interactions may play a deleterious as well as beneficial role in stroke recovery. Furthermore, they may provide a novel way to approach potential therapies, since current stroke drug therapy is limited to only one Food and Drug Administration-approved drug complicated by a narrow therapeutic window. Until this point, most research has emphasized neuroimmune interactions, but little focus has been on bidirectional communication of glial–immune interactions in the ischemic brain. By expanding our understanding of these interactions through a compilation of glial cell effects, we may be able to pinpoint major modulating factors in brain homeostasis to maintain or discover ways to suppress irreversible ischemic damage and improve brain repair.