Systemic infection, inflammation and acute ischemic stroke.
ABSTRACT Extensive evidence implicates inflammation in multiple phases of stroke etiology and pathology. In particular, there is growing awareness that inflammatory events outside the brain have an important impact on stroke susceptibility and outcome. Numerous conditions, including infection and chronic non-infectious diseases, that are established risk factors for stroke are associated with an elevated systemic inflammatory profile. Recent clinical and pre-clinical studies support the concept that the systemic inflammatory status prior to and at the time of stroke is a key determinant of acute outcome and long-term prognosis. Here, we provide an overview of the impact of systemic inflammation on stroke susceptibility and outcome. We discuss potential mechanisms underlying the impact on ischemic brain injury and highlight the implications for stroke prevention, therapy and modeling.
SourceAvailable from: Yvonne Couch[Show abstract] [Hide abstract]
ABSTRACT: IntroductionSystemic inflammation has been shown to significantly worsen the outcome of neurological disease. However, after acute injuries to the brain both pre- and post-conditioning with bacterial endotoxin has been shown to reduce leukocyte recruitment to the CNS. Here, we sought to determine whether viral pre-challenge would have an effect on the outcome of acute CNS inflammation that was distinct from endotoxin.Methods Animals received a single intracranial microinjection of IL-1ß in the presence or absence of a viral pre-challenge 24 hours prior to surgery. Liver and brain tissue were analysed for chemokine expression by qRT-PCR and leukocyte and monocyte infiltration 12 hours, 3 days and 7 days after the IL-1ß injection.ResultsHere, a single injection of adenovirus prior to IL-1ß injection resulted in adhesion molecule expression, chemokine expression and the recruitment of neutrophils to the injured CNS in significantly higher numbers than in IL-1ß injected animals. The distribution and persistence of leukocytes within the CNS was also greater after pre-challenge, with neutrophils being found in both the ipsilateral and contralateral hemispheres. Thus, despite the absence of virus within the CNS, the presence of virus within the periphery was sufficient to exacerbate CNS disease.Conclusions These data suggest that the effect of a peripheral inflammatory challenge on the outcome of CNS injury or disease is not generic and will be highly dependent on the nature of the pathogen.Journal of Neuroinflammation 10/2014; 11(1):178. DOI:10.1186/s12974-014-0178-3 · 4.90 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Background: Some studies have suggested an association between Helicobacter pylori infection and the risk of stroke, but the relationship remains controversial. The aim of this study was to obtain a more comprehensive estimate of H. pylori on the risk of stroke by performing a meta-analysis. Methods: A computerized search of PubMed, EMBASE, and the Cochrane library (including CENTRAL) up to February 2014 was performed to identify eligible studies. Prospective studies reported that a multivariate-adjusted estimate for the association between H. pylori and stroke were included. A random-effects model was used to calculate the overall combined risk. Results: Ten prospective observational studies (6 cohort studies, 4 nested case-control, or case-cohort studies within cohort studies) were included in the meta-analysis. The overall combined odds ratio for H. infection and stroke was .96 (95% confidence interval, .78-1.14). Similar results were yielded in patients with cytotoxin-associated gene-A seropositive strains. The combined estimates were robust across sensitivity analyses and had no observed publication bias. Conclusions: In conclusion, our formal meta-analysis indicated no strong association between H. pylori infection and stroke, neither in those with cytotoxin-associated gene-A-positive infection. We believe that future epidemiologic studies of H. pylori and stroke are unlikely to be fruitful.Journal of Stroke and Cerebrovascular Diseases 10/2014; 23(9):2233-9. DOI:10.1016/j.jstrokecerebrovasdis.2014.04.020 · 1.99 Impact Factor
Article: Interleukin-1 and acute brain injury[Show abstract] [Hide abstract]
ABSTRACT: Inflammation is the key host-defense response to infection and injury, yet also a major contributor to a diverse range of diseases, both peripheral and central in origin. Brain injury as a result of stroke or trauma is a leading cause of death and disability worldwide, yet there are no effective treatments, resulting in enormous social and economic costs. Increasing evidence, both preclinical and clinical, highlights inflammation as an important factor in stroke, both in determining outcome and as a contributor to risk. A number of inflammatory mediators have been proposed as key targets for intervention to reduce the burden of stroke, several reaching clinical trial, but as yet yielding no success. Many factors could explain these failures, including the lack of robust preclinical evidence and poorly designed clinical trials, in addition to the complex nature of the clinical condition. Lack of consideration in preclinical studies of associated co-morbidities prevalent in the clinical stroke population is now seen as an important omission in previous work. These co-morbidities (atherosclerosis, hypertension, diabetes, infection) have a strong inflammatory component, supporting the need for greater understanding of how inflammation contributes to acute brain injury. Interleukin (IL)-1 is the prototypical pro-inflammatory cytokine, first identified many years ago as the endogenous pyrogen. Research over the last 20 years or so reveals that IL-1 is an important mediator of neuronal injury and blocking the actions of IL-1 is beneficial in a number of experimental models of brain damage. Mechanisms underlying the actions of IL-1 in brain injury remain unclear, though increasing evidence indicates the cerebrovasculature as a key target. Recent literature supporting this and other aspects of how IL-1 and systemic inflammation in general contribute to acute brain injury are discussed in this review.Frontiers in Cellular Neuroscience 03/2015; 9. DOI:10.3389/fncel.2015.00018 · 4.18 Impact Factor