Splenic responses in ischemic stroke: new insights into stroke pathology

Abstract

In the past decade, the significant contribution of the spleen to ischemic brain damage has gained considerable attention in stroke research. As the largest natural reservoir of immune cells, the spleen establishes critical connections with the ischemic brain during the progression of stroke and mobilizes its cells to the site of injury. Multiple "alarm" signals released from the injured brain are essential for the initiation of brain-spleen communication. Spleen-derived cells, including neutrophils, lymphocytes, and monocytes/macrophages, are known to contribute significantly to ischemic brain damage. Understanding the dynamic splenic responses to stroke will not only provide insights into the evolvement of ischemic brain injury but will also identify potential targets for stroke treatment. Here, we review recent studies on the functions of the spleen in ischemic stroke. We have included a discussion of several therapeutic strategies that target splenic responses and reduce acute ischemic brain damage in preclinical studies. Future investigations on the effects of the spleen on long-term stroke recovery are highly warranted.

Keywords: Immune response; Spleen; Stroke; Therapeutic strategies.

Figure 1

Spleen–brain communication after stroke. The ischemic brain stimulates the autonomic nervous system and releases chemotactic factors or CNS antigens to trigger the efflux of immune cells from the spleen to the site of brain injury. At the site of injury, inflammatory cells migrate through the compromised blood–brain barrier and enter the brain with a large amount of chemokines/cytokines, free radicals, and other inflammatory mediators. These factors are thought to exacerbate brain injury in the acute phases of stroke.