Systemic infection, inflammation and acute ischemic stroke

Faculty of Life Sciences, Michael Smith Building, University of Manchester, Manchester M13 9PT, UK.
Neuroscience (Impact Factor: 3.36). 09/2008; 158(3):1049-61. DOI: 10.1016/j.neuroscience.2008.08.019
Source: PubMed


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.

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    • "The immunology of stroke and its relation to fatigue There is increasing evidence that inflammation plays an important role in acute ischemic stroke (AIS), indicating important interactions between the nervous and immune systems [16] [17]. Cerebral ischemia induces a strong inflammatory reaction that involves several cell types. "
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    ABSTRACT: Poststroke fatigue (PSF) and poststroke depression (PSD) are both common and difficult sequelae following acute ischemic stroke (AIS). Two main perspectives to explain these sequelae are the biomedical perspective and the psychosocial perspective. Research has shown that PSF and PSD are undoubtedly associated with each other, although each can occur in the absence of the other. However, the nature of the relationship is unclear. For example, do stroke patients become fatigued because of being depressed, or do they become depressed because they are fatigued? Alternatively, is there a bidirectional relationship between these two sequelae, with each influencing the other? We propose a biopsychosocial model of PSF and PSD that supports the AIS-induced immune response and kynurenine pathway activation being related to fatigue but not (directly) to depression. We hypothesize that the risk of developing depression may be reduced if the experience of fatigue is acknowledged, and then addressed accordingly.
    Medical Hypotheses 10/2015; 85(6). DOI:10.1016/j.mehy.2015.10.001 · 1.07 Impact Factor
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    • "A review and meta-analysis from 2012 of biomarkers for acute stroke (Hasan et al. 2012) concluded that while the identified biomarkers are likely to be biologically informative with respect to the mechanisms underlying vascular disease, their clinical potential as a blood-based test warrants further investigation. AIS is a complex neurobiological process (Brouns and De Deyn 2009) that is associated with inflammation (Jin et al. 2010; McColl et al. 2009; Ormstad et al. 2011b; Vogelgesang et al. 2014) and oxidative stress (Love 1999; Manzanero et al. 2013; Nanetti et al. 2007; Taffi et al. 2008). "
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    ABSTRACT: Fast diagnosis and appropriate treatment are of utmost importance to improving the outcome in patients with acute ischemic stroke (AIS). A rapid and sensitive blood test for ischemic stroke is required. The aim of this study was to examine the usefulness of phenylalanine (PHE) and tyrosine (TYR) as diagnostic biomarkers in AIS. Serum levels of PHE and TYR, measured using HPLC, and their ratio (PHE/TYR) were compared between 45 patients with AIS and 40 healthy control subjects. The relationship between PHE/TYR and the serum levels of several cytokines were also examined. PHE/TYR was significantly higher in AIS patients than in healthy controls (1.75 vs 1.24, p < 0.001). A receiver operating characteristic (ROC) curve analysis of PHE/TYR in AIS patients relative to healthy controls revealed promising sensitivity and specificity, which at an optimal cutoff of 1.45 were 76 and 85 %, respectively. PHE/TYR was positively correlated with interleukin (IL)-1β (r = 0.37, p = 0.011) and IL-6 (r = 0.33, p = 0.025). This study shows that PHE/TYR is highly elevated in the acute phase of AIS, and that this elevation is coupled to the inflammatory response. The ROC analysis documents the possible value of PHE/TYR as a biomarker for AIS and demonstrates its clinical potential as a blood-based test for AIS.
    Journal of Molecular Neuroscience 10/2015; DOI:10.1007/s12031-015-0659-6 · 2.34 Impact Factor
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    • "and elevated levels of IL-1 can also affect patient susceptibility and severity of CNS injury (McColl et al., 2009; Denes et al., 2010). The overwhelming majority of patients presenting with ischemic or hemorrhagic stroke have one or more risk factors including obesity, hypertension, atherosclerosis, diabetes and infection, which account for 60–80% of stroke risk in the general population (Hankey, 2006; Emsley and Hopkins, 2008). "
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    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 · 4.29 Impact Factor
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