Neuroinflammatory Mechanisms in Ischemic Stroke: Focus on Cardioembolic Stroke, Background, and Therapeutic Approaches

Abstract

One of the most important causes of neurological morbidity and mortality in the world is ischemic stroke. It can be a result of multiple events such as embolism with a cardiac origin, occlusion of small vessels in the brain, and atherosclerosis affecting the cerebral circulation. Increasing evidence shows the intricate function played by the immune system in the pathophysiological variations that take place after cerebral ischemic injury. Following the ischemic cerebral harm, we can observe consequent neuroinflammation that causes additional damage provoking the death of the cells; on the other hand, it also plays a beneficial role in stimulating remedial action. Immune mediators are the origin of signals with a proinflammatory position that can boost the cells in the brain and promote the penetration of numerous inflammatory cytotypes (various subtypes of T cells, monocytes/macrophages, neutrophils, and different inflammatory cells) within the area affected by ischemia; this process is responsible for further ischemic damage of the brain. This inflammatory process seems to involve both the cerebral tissue and the whole organism in cardioembolic stroke, the stroke subtype that is associated with more severe brain damage and a consequent worse outcome (more disability, higher mortality). In this review, the authors want to present an overview of the present learning of the mechanisms of inflammation that takes place in the cerebral tissue and the role of the immune system involved in ischemic stroke, focusing on cardioembolic stroke and its potential treatment strategies.

Keywords: cardiac embolism; ischemic stroke; neuroinflammation.

Figure 1

Pathomechanism of ischemic brain damage.

Figure 2

Activated microglia have two activation phenotypes: classically activated (M1) and alternatively activated (M2). M1 microglia are considered as proinflammatory and produce proinflammatory cytokines and oxidative metabolites such as IL-1β, TNF-α, IL-6, and nitric oxide. M2 microglia contribute to recovery after brain injury, are activated by IL-4, and express anti-inflammatory mediators, such as IL-10, IL-4, and TGF-β. IL: interleukin; TNF: tumor necrosis factor; TGF: transforming growth factor.

Figure 3

T cells involvement in acute ischemic stroke.