The impact of lesion location and lesion size on poststroke infection frequency

Minnerup, Jens; Wersching, Heike; Brokinkel, Benjamin; Dziewas, Rainer; Heuschmann, Peter U.; Nabavi, Darius G.; Ringelstein, E. B.; Schäbitz, Wolf‐Rüdiger; Ritter, Martin

doi:10.1136/jnnp.2009.182394

Cited by 52 publications

(48 citation statements)

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“…Moreover, the extent of brain damage (large infarctions vs small infarctions) might have differentially influenced the function of Tregs and, therefore, stroke outcome. [41][42][43] Finally, Liesz et al predominantly focused on the contribution of Tregs for tissue reorganization and repair at later stages of infarct development, 7 whereas our study above all was intended to analyze the acute effects of Tregs in stroke pathogenesis. 44 and diphtheria toxin injection did not lead to a loss of epithelial integrity in the DEREG model, making the "nonimmune" effects of diphtheria toxin treatment in the tMCAO model unlikely.…”

Section: Discussionmentioning

confidence: 99%

Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature

Kleinschnitz

Kraft

Dreykluft

et al. 2013

Blood

308

293

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Key Points• Regulatory T cells are promoters of ischemic stroke by inducing dysfunction of the cerebral microvasculature. We have recently identified T cells as important mediators of ischemic brain damage, but the contribution of the different T-cell subsets is unclear. Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) are generally regarded as prototypic antiinflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. In the present study, we examined the role of Tregs after experimental brain ischemia/reperfusion injury. Selective depletion of Tregs in the DEREG mouse model dramatically reduced infarct size and improved neurologic function 24 hours after stroke and this protective effect was preserved at later stages of infarct development. The specificity of this detrimental Treg effect was confirmed by adoptive transfer experiments in wild-type mice and in IntroductionIschemic stroke induces a profound local inflammatory response involving various types of immune cells that transmigrate across the activated blood-brain barrier to invade the brain in a timed fashion. 1 Although previous research mainly focused on the role of innate immune cells, 2 recent evidence suggests that T cells, which belong to the adaptive immune system, also contribute critically to stroke development, especially in the early phase. 3 T cells have been identified in the postischemic brain as soon as 24 hours after reperfusion, 4 and Abs directed against vascular adhesion receptors expressed on the brain endothelium or leukocyte very late antigen-4 (VLA-4) expressed on lymphocytes inhibited T-cell transmigration and reduced tissue damage in models of stroke. 5 We and others showed recently that recombination activating gene (Rag1)-deficient mice, which lack functional T cells, are largely resistant against ischemic neurodegeneration. 6-8 T cellmediated brain damage became manifest by 24 hours after transient middle cerebral artery occlusion (tMCAO) and did not depend on antigen recognition or costimulation. 8 This clearly argues against TCR-driven mechanisms of tissue damage and suggests instead that T cells act detrimentally in ischemic stroke through antigenindependent pathways, at least during the early phase. Moreover, Rag1 Ϫ/Ϫ mice did not display a gross defect in thrombus formation after artificial vessel wall injury, which could easily explain the stroke protective phenotype in these animals. 8 Although the deleterious effects of T cells in stroke pathophysiology are well accepted, the functional relevance of the different T-cell subsets for stroke progression is less clear, as is their pathologic contribution at the different stages of cerebral ischemia (ie, acute versus chronic). Using adoptive cell transfer in Rag1 Ϫ/Ϫ mice, we could demonstrate that natural killer T cells (NKT cells) Submitted April 26, 2012; accepted October 27, 2012.Prepublished online as Blood First Edition paper, November 15, 2012; DOI 10.1182/blood-2012-04-426734. *C.K. and P.K. ...

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Section: Discussionmentioning

confidence: 99%

Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature

Kleinschnitz

Kraft

Dreykluft

et al. 2013

Blood

308

293

View full text Add to dashboard Cite

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“…The majority of SAP studies have been performed in stroke units or in mixed acute settings. The incidence of SAP among the majority of studies that have been performed exclusively in stroke units ranged between 3.9 and 12% [1,3,17,24,59,60,61,62,63,64,65,66,67] except for one study where the incidence was 44% [25]. This could reflect a selection bias since all patients included in this study had nasogastric tube feeding, higher rate of mechanical ventilation (18%) and their strokes were more severe [mean baseline National Institutes of Health Stroke Scale (NIHSS) score = 13.4].…”

Section: Incidence Of Sapmentioning

confidence: 99%

Stroke-Associated Pneumonia: Major Advances and Obstacles

et al. 2013

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Background: Stroke-associated pneumonia (SAP) has been implicated in the morbidity, mortality and increased medical cost after acute ischemic stroke. The annual cost of SAP during hospitalization in the United States approaches USD 459 million. The incidence and prognosis of SAP among intensive care unit (ICU) patients have not been thoroughly investigated. We reviewed the pathophysiology, microbiology, incidence, risk factors, outcomes and prophylaxis of SAP with special attention to ICU studies. Methods: To determine the incidence, risk factors and prognosis of acute SAP, PubMed was searched using the terms ‘pneumonia' AND ‘neurology intensive unit' and the MeSH terms ‘stroke' AND ‘pneumonia'. Non-English literature, case reports and chronic SAP studies were excluded. Studies were classified into 5 categories according to the setting they were performed in: neurological intensive care units (NICUs), medical intensive care units (MICUs), stroke units, mixed studies combining more than one setting or when the settings were not specified and rehabilitation studies. Results: The incidences of SAP in the following settings were: NICUs 4.1-56.6%, MICUs 17-50%, stroke units 3.9-44%, mixed studies 3.9-23.8% and rehabilitation 3.2-11%. The majority of NICU and MICU studies were heterogeneous including different neurovascular diseases, which partly explains the wide range of SAP incidence. The higher incidence in the majority of ICU studies compared to stroke units or acute floor studies is likely explained by the presence of mechanical ventilation, higher stroke severity causing higher rates of aspiration and stroke-induced immunodepression among ICU patients. The short-term mortality of SAP was increased among the mixed and stroke unit studies ranging between 10.1 and 37.3%. SAP was associated with worse functional outcome in the majority of stroke unit and floor studies. Mortality was less consistent among NICU and MICU studies. This difference could be due to the heterogeneity of ICU studies and the effect of small sample size or other independent risk factors for mortality such as the larger neurological deficit, mechanical ventilation, and age, which may simultaneously increase the risk of SAP and mortality confounding the outcomes of SAP itself. The pathophysiology of SAP is likely explained by aspiration combined with stroke-induced immunodepression through complex humeral and neural pathways that include the hypothalamic-pituitary-adrenal axis, parasympathetic and sympathetic systems. Conclusions: A unified definition of SAP, strict inclusion criteria, and the presence of a long-term follow-up need to be applied to the future prospective studies to better identify the incidence and prognosis of SAP, especially among ICU patients.

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“…8,9 Prophylactic antibiotics poststroke were shown to lower the frequency of infections. However, results on functional recovery of studies using this approach are conflicting.…”

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confidence: 99%

“…Established risk factors for poststroke infections include dysphagia, large infarcts, and monocytic HLA-DR expression. 8,11,13 Sleep-related breathing disorders such as obstructive and central sleep apnea are also relevant complications in the The opinions in this editorial are not necessarily those of the editors or of the American Heart Association.…”

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confidence: 99%