Immune interventions in stroke

After an ischaemic or haemorrhagic stroke, microglial activation and the release of cell death products initiate a chain of inflammatory events that lead to vascular damage and oedema. Here, Shi and colleagues discuss the similarities between acute stroke and multiple sclerosis, and review past attempts to limit poststroke inflammation via immunotherapy. The authors then highlight gaps in our knowledge about the immune system's reaction to stroke, and discuss how best to move forward with this line of research. Approaches for the effective management of acute stroke are sparse, and many measures for brain protection fail. However, our ability to modulate the immune system and modify the progression of multiple sclerosis is increasing. As a result, immune interventions are currently being explored as therapeutic interventions in acute stroke. In this Review, we compare the immunological features of acute stroke with those of multiple sclerosis, identify unique immunological features of stroke, and consider the evidence for immune interventions. In patients with acute stroke, microglial activation and cell death products trigger an inflammatory cascade that damages vessels and the parenchyma within minutes to hours of the ischaemia or haemorrhage. Immune interventions that restrict brain inflammation, vascular permeability and tissue oedema must be administered rapidly to reduce acute immune-mediated destruction and to avoid subsequent immunosuppression. Preliminary results suggest that the use of drugs that modify disease in multiple sclerosis might accomplish these goals in ischaemic and haemorrhagic stroke. Further elucidation of the immune mechanisms involved in stroke is likely to lead to successful immune interventions.