Spleen-derived immune cells potentiate cerebral ischemia-reperfusion injury through brain-spleen communication

Immune and inflammatory responses play a major role in cerebral ischemia-reperfusion injury (CIRI). The spleen participates in the regulation of immune and inflammatory responses. However, the exact mechanism through which the spleen participates in CIRI remains unclear. The goal of this study is to explore the brain-spleen communication mechanism in CIRI.

Transient middle cerebral artery occlusion model (tMCAO) was performed in rats. Dynamic observation of brain injury severity was performed using neurological function scoring and TTC staining. Changes in spleen morphology, immune cells in spleen and brain infiltrating immune cells were observed by weighing method and flow cytometry. Subsequently, the splenectomy experiments further confirmed the role of immune cells as intermediaries in brain-spleen communication.

The results demonstrated that the spleen exhibited a biphasic "V"-shaped curve, characterized by marked atrophy during the acute phase followed by a return to baseline levels. This change was significantly correlated with the degree of brain injury. Flow cytometry and correlation analysis showed that splenic atrophy was accompanied by the release of splenic T cells and NKT cells into brain tissue, exacerbating neuroinflammatory responses. After splenectomy, the proportion of immune cells in the brain tissue decreased, and the degree of brain injury was significantly reduced.

Our research results indicate that the spleen initially contracts and then expands after CIRI, and mediates ischemic brain injury through immune cells. Thus, focusing on indirect spleen regulation in future studies will provide a new perspective for the treatment of inflammation after CIRI.