Perspectives on effect of spleen in ischemic stroke

Abstract

Despite decades of research, stroke therapies are limited to recanalization therapies that can only be used on <10% of stroke patients; the vast majority of stroke patients cannot be treated by these methods. Even if recanalization is successful, the outcome is often poor due to subsequent reperfusion injury. A major damage mechanism operating in stroke is inflammatory injury due to excessive pro-inflammatory cascades. Many studies have shown that, after stroke, splenic inflammatory cells, including neutrophils, monocytes/macrophages, and lymphocytes, are released and infiltrate the brain, heightening brain inflammation, and exacerbating ischemia/reperfusion injury. Clinical studies have observed spleen contraction in acute stroke patients where functional outcome improved with the gradual recovery of spleen volume. These observations are supported by stroke animal studies that have used splenectomy- or radiation-induced inhibition of spleen function to show spleen volume decrease during the acute phase of middle cerebral artery occlusion, and transfer of splenocytes to stroke-injured brain areas. Thus, activation and release of splenic cells are upstream of excessive brain inflammation in stroke. The development of reversible means of regulating splenic activity offers a therapeutic target and potential clinical treatment for decreasing brain inflammation and improving stroke outcomes.