The Immune System in Stroke: Clinical Challenges and Their Translation to Experimental Research

Abstract

Stroke represents an unresolved challenge for both developed and developing countries and has a huge socio-economic impact. Although considerable effort has been made to limit stroke incidence and improve outcome, strategies aimed at protecting injured neurons in the brain have all failed. This failure is likely to be due to both the incompleteness of modelling the disease and its causes in experimental research, and also the lack of understanding of how systemic mechanisms lead to an acute cerebrovascular event or contribute to outcome.Inflammation has been implicated in all forms of brain injury and it is now clear that immune mechanisms profoundly influence (and are responsible for the development of) risk and causation of stroke, and the outcome following the onset of cerebral ischemia. Until very recently, systemic inflammatory mechanisms, with respect to common comorbidities in stroke, have largely been ignored in experimental studies. The main aim is therefore to understand interactions between the immune system and brain injury in order to develop novel therapeutic approaches. Recent data from clinical and experimental research clearly show that systemic inflammatory diseases -such as atherosclerosis, obesity, diabetes or infectionsimilar to stress and advanced age, are associated with dysregulated immune responses which can profoundly contribute to cerebrovascular inflammation and injury in the central nervous system. In this review, we summarize recent advances in the field of inflammation and stroke, focusing on the challenges of translation between pre-clinical and clinical studies, and potential anti-inflammatory/immunomodulatory therapeutic approaches.

Circulating CD40 + and CD86 + B Cell Subsets Demonstrate Opposing Associations With Risk of Stroke

“…36 Inflammation and immune mechanisms have been found to influence the pathogenesis of atherosclerosis and coronary artery disease as well as the risk and causation of stroke. 47,48 The discrepancies found in the present study that only stroke and not coronary artery disease was associated with the B cell subsets may reflect the heterogeneous pathogenesis of stroke. High numbers of CD19 49 IL-21 was found to expand IL-10-producing regulatory B cells several fold, resulting in increased inhibition of experimental autoimmune disease, making analyses of this cytokine a target of great interest in future studies.…”

Association between previously diagnosed circulatory conditions and a dietary inflammatory index

“…However, the DII is a tool that measures the inflammatory potential of diet. Inflammation is a substrate for a number of primary mechanisms through which circulatory disorders develop and progress [1–3]. Additionally, the DII has been associated with ‘less healthy’ (e.g., Western) diets in previous simulation analyses [35].…”

“…Chronic inflammation is an underlying pathophysiological process associated with numerous chronic conditions including cancer, diabetes, circulatory disease (e.g., cardiovascular [CVD] or cerebrovascular disease), metabolic syndrome (MetSyn), and both disease-specific and overall mortality [1]. Inflammation is a key component throughout the atherosclerotic process [2], as well as in the triggering of events such as stroke or myocardial infarction [3, 4]. Dietary patterns consistently have been shown to be strong moderators of systemic inflammation [5].…”

Carvacrol protects neuroblastoma SH-SY5Y cells against Fe2+-induced apoptosis by suppressing activation of MAPK/JNK-NF-κB signaling pathway

“…Therefore, the toxicity of iron overload is often associated with inflammation, which is involved in pathogenic effects, including damage to neurons [9] . It has been reported that the production of proinflammatory cytokines, such as IL-1β, IL-6 and TNF-α is upregulated following ischemia and intracerebral hemorrhage, which results in neuroinflammation [10,11] . These cytokines are key mediators of npg inflammatory responses, and their overexpression can further activate downstream apoptotic signaling pathways in neurons, which ultimately results in neuronal death [12] .…”