Inflammation and Infections as Risk Factors for Ischemic Stroke

Abstract

Background-Inflammatory processes have fundamental roles in stroke in both the etiology of ischemic cerebrovascular disease and the pathophysiology of cerebral ischemia. We summarize clinical data on infection and inflammation as risk or trigger factors for human stroke and investigate current evidence for the hypothesis of a functional interrelation between traditional risk factors, genetic predisposition, and infection/inflammation in stroke pathogenesis. Summary of Review-Several traditional vascular risk factors are associated with proinflammatory alterations, including leukocyte activation, and predispose cerebral vasculature to thrombogenesis on inflammatory stimulation. Furthermore, accumulation of inflammatory cells, mainly monocytes/macrophages, within the vascular wall starts early during atherogenesis. During later disease stages, their activation can lead to plaque rupture and thrombus formation, increasing stroke risk. Inflammatory markers (eg, leukocytes, fibrinogen, C-reactive protein) are independent predictors of ischemic stroke. Chronic infections (eg, infection with Chlamydia pneumoniae or Helicobacter pylori) were found to increase the risk of stroke; however, study results are at variance, residual confounding is not excluded, and causality is not established at present. In case-control studies, acute infection within the preceding week was a trigger factor for ischemic stroke. Acute and exacerbating chronic infection may act by activating coagulation and chronic infections and may contribute to atherogenesis. Genetic predisposition of the inflammatory host response may be an important codeterminant for atherogenesis and stroke risk. Conclusions-Inflammation contributes to stroke risk via various interrelated mechanisms. Infectious diseases, traditional risk factors, and genetic susceptibility may cooperate in stimulating inflammatory pathways. Final proof of a causal role of infectious/inflammatory mechanisms in stroke pathogenesis is still lacking and will require interventional studies.

The etiology of poststroke depression: a review of the literature and a new hypothesis involving inflammatory cytokines

“…Several studies have reported prominent changes in proinflammatory cytokines following stroke. [20][21][22] The proinflammatory cytokines interleukin (IL)-1, tumor necrosis factor a (TNF-a), IL-6 and IL-8 have all been shown to be involved in the initiation or amplification of the inflammatory response in patients following acute cerebral ischemia. Interestingly for our purposes, some studies on experimental models have suggested that inflammatory mediators, such as the cytokine IL-1, might contribute to the extent of cerebral ischemia through their effects on specific limbic pathways.…”

Inverse correlation between cerebral blood flow measured by continuous arterial spin-labeling (CASL) MRI and neurocognitive function in children with sickle cell anemia (SCA)

“…To our knowledge, an association between WBC count and IQ has not been described previously, although increased WBC count at baseline was associated with increased risk of early death in a large cohort study of SCA. 17 WBC count may serve as a marker of inflammatory mediators, which have been associated with increased risk of stroke and cognitive impairment in adults, 18 or of decreased splenic function and severe disease in SCA. 1 …”

Upregulated expression of S100A8 in mice brain after focal cerebral ischemia reperfusion

“…[1] Recent studies have showed that S100A8 has been implicated in the pathobiology of inflammatory disorders, such as asthma, rheumatoid arthritis, and inflammatory bowel disease. [2] It is well known that the inflammatory and immune reactions are involved in cerebral ischemia reperfusion (I/R),[3,4] but whether S100A8 mediates the injury in the process of cerebral I/R is still unknown. We here report our findings concerning the expression changes and the role of S100A8 in cerebral I/R.…”