Immunology of Ischemic Stroke: Impact, Mechanisms, and Immunomodulatory Therapies

It is increasingly recognized that ischemic stroke is not only a brain disease characterized by brain cell death and damage but is also marked by the dysfunction of immune organs, as evidenced by systematic immune dysregulation prior to or after cerebral ischemia. For instance, with the prevalence of comorbidities such as diabetes, obesity, and hypertension, pre-existing chronic systematic inflammation has been considered an essential contributor that exacerbates stroke pathology. Conversely, mild immune responses induced by preconditioning have also been shown to protect against cerebral ischemic injury. Moreover, once stroke occurs, the injured brain evokes immune responses both in the brain and in the peripheral by communicating with the immune system via danger-associated molecular patterns or antigens, cytokines, and chemokines as well as via specific neural circuits, such as the sympathetic and parasympathetic nervous system. This bidirectional communication between the injured brain and the immune system determines the progression of acute infarct damage, long-term tissue repair, as well as postischemic systematic immunosuppression. In summary, the pre-existing immune responses as well as the immune responses evoked by cerebral ischemia play essential roles in shaping stroke outcomes. The therapies that target the immune responses, especially the immunomodulatory therapies, are promising treatments for ischemic stroke.