Systemic inflammation in hemorrhagic strokes – A novel neurological sign and therapeutic target?

Growing evidences suggest that stroke is a systemic disease affecting many organ systems beyond the brain. Stroke-related systemic inflammatory response and immune dysregulations may play an important role in brain injury, recovery, and stroke outcome. The two main phenomena in stroke-related peripheral immune dysregulations are systemic inflammation and post-stroke immunosuppression. There is emerging evidence suggesting that the spleen contracts following ischemic stroke, activates peripheral immune response and this may further potentiate brain injury. Whether similar brain–immune crosstalk occurs in hemorrhagic strokes such as intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) is not established. In this review, we systematically examined animal and human evidence to date on peripheral immune responses associated with hemorrhagic strokes. Specifically, we reviewed the impact of clinical systemic inflammatory response syndrome (SIRS), inflammation- and immune-associated biomarkers, the brain–spleen interaction, and cellular mediators of peripheral immune responses to ICH and SAH including regulatory T cells (Tregs). While there is growing data suggesting that peripheral immune dysregulation following hemorrhagic strokes may be important in brain injury pathogenesis and outcome, details of this brain-immune system cross-talk remain insufficiently understood. This is an important unmet scientific need that may lead to novel therapeutic strategies in this highly morbid condition.