Neuroinflammation in Ischemic Stroke: Mechanisms, Systemic Interactions, and Therapeutic Targets.

Ischemic stroke is the second leading cause of death worldwide and its global burden is predicted to increase over the upcoming decades. Acute therapies primarily focus on recanalization of the occluded blood vessels by intravenous thrombolysis and endovascular thrombectomy, but these therapies are not suitable for all patients. Also, in case of successful reperfusion, there remains a risk of secondary tissue damage known as ischemia-reperfusion injury. Inflammation plays a crucial role in both the infarcted tissue and ischemia-reperfusion injury after stroke. Innate and adaptive immune systems may drive an exacerbated inflammatory response after stroke, impacting patients' outcome. Research in stroke pathophysiology and the role of the immune system after stroke suggests that outcome may be improved by using immune-based therapies preventing this secondary tissue damage. Here we display a comprehensive description of chronological immune events at the cellular and molecular levels in different compartments after stroke and discuss the potential neuroprotective role of regulatory T cells (Tregs). We connect both anti and pro-inflammatory cascades in parallel within different body compartments over time and explore the potential for manipulation of specific immune events to develop new therapies.