Brain Immune Interactions—Novel Emerging Options to Treat Acute Ischemic Brain Injury

Abstract

Ischemic stroke is still among the leading causes of mortality and morbidity worldwide. Despite intensive advancements in medical sciences, the clinical options to treat ischemic stroke are limited to thrombectomy and thrombolysis using tissue plasminogen activator within a narrow time window after stroke. Current state of the art knowledge reveals the critical role of local and systemic inflammation after stroke that can be triggered by interactions taking place at the brain and immune system interface. Here, we discuss different cellular and molecular mechanisms through which brain–immune interactions can take place. Moreover, we discuss the evidence how the brain influence immune system through the release of brain derived antigens, damage-associated molecular patterns (DAMPs), cytokines, chemokines, upregulated adhesion molecules, through infiltration, activation and polarization of immune cells in the CNS. Furthermore, the emerging concept of stemness-induced cellular immunity in the context of neurodevelopment and brain disease, focusing on ischemic implications, is discussed. Finally, we discuss current evidence on brain–immune system interaction through the autonomic nervous system after ischemic stroke. All of these mechanisms represent potential pharmacological targets and promising future research directions for clinically relevant discoveries.

Risk factors, clinical features, and outcomes of patients with hypertrophic cardiomyopathy complicated by ischemic stroke: A single-center retrospective study

“…The role of inflammation in IS has drawn great attention since neuronal death caused by occlusion of cerebral blood flow can trigger both local and systemic immune responses ( 35 , 36 ). Accordingly, individuals with signs of inflammation or corresponding biomarkers have an increased risk of stroke ( 37 ).…”

Interplay between Gut Microbiota and NLRP3 Inflammasome in Intracerebral Hemorrhage

“…Once the intestinal mucosa is damaged, the number and structure of the intestinal flora will change immediately. Previous studies found that the gut microbiota changed significantly through the brain-gut axis after ICH [38] (Table 2). After stroke, activated microglia and injured brain tissue release DAMPs and cytokines, leading to endothelial cell activation and the expression of chemokines and adhesion molecules, which further promote the recruitment of immune and inflammatory cells from the bloodstream to the damaged site in the brain [39].…”

The mechanism of microglia-mediated immune inflammation in ischemic stroke and the role of natural botanical components in regulating microglia: A review

“…DAMPs can promote the interaction between APCs and receptors to activate adaptive immune responses, which are mediated by effector T cells ( 47 ). Effector T cells play a role in the adaptive immune response by recruiting to ischemic areas, traversing the injured BBB, releasing inflammatory cytokines such as interferon gamma (IFN-γ) in the brain parenchyma, and ultimately leading to delayed neurotoxicity ( 39 , 48 ). The immune response after IS is a self-limiting pathophysiological process that gradually subsides under the combined action of regulatory T cells and B cells, preparing for the structural and functional reconstruction of the later brain injury site.…”