Dataset Information

Persistent inflammation worsens short-term outcomes in massive stroke patients.

ABSTRACT:

Background

Persistent inflammation is an important driver of disease progression and affects prognosis. Some indicators of inflammation predict short-term outcomes. The relationship between prognosis, especially mortality, and persistent inflammation in massive stroke has not been studied, and this has been the subject of our research.

Methods

From April 1, 2017 to February 1, 2020, consecutive patients were prospectively enrolled. Clinical data, laboratory data, imaging data and follow-up infections morbidity were compared between 2 groups according to modified Rankin scale (mRS) scores (mRS?ResultsOne hundred thirty-nine patients with massive stroke were included from 800 patients. We found that admission blood glucose levels (p?=?0.005), proportions of cerebral hemispheric (p?=?0.001), posterior circulatory (p?=?0.035), and lacunar (p?=?0.022) ischemia were higher in poor outcome patients; neutrophil-to-lymphocyte ratio (odd ratio?=?1.87, 95%CI 1.14-3.07, p?=?0.013) and blood glucose concentrations (odd ratio?=?1.34, 95%CI 1.01-1.79, p?=?0.043) can independently predict the short-term prognosis in massive stroke patients. We also found that the incidence of pulmonary infection (p?=?0.009), one-month mortality (p?=?0.003) and adverse outcomes (p?=?0.0005) were higher in patients with persistent inflammation.

Conclusions

This study suggested that persistent inflammation is associated with poor prognosis, 1-month mortality and the occurrence of in-hospital pulmonary infection and that higher baseline inflammation level predicts short-term poor outcomes in massive stroke.

SUBMITTER: Hou D

PROVIDER: S-EPMC7874622 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Persistent inflammation worsens short-term outcomes in massive stroke patients.

Hou Duanlu D Wang Chunjie C Ye Xiaofei X Zhong Ping P Wu Danhong D

BMC neurology 20210210 1

<h4>Background</h4>Persistent inflammation is an important driver of disease progression and affects prognosis. Some indicators of inflammation predict short-term outcomes. The relationship between prognosis, especially mortality, and persistent inflammation in massive stroke has not been studied, and this has been the subject of our research.<h4>Methods</h4>From April 1, 2017 to February 1, 2020, consecutive patients were prospectively enrolled. Clinical data, laboratory data, imaging data and ...[more]

PMID: 33568099

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Project description:RationaleCurrently, there is no effective intervention available that can reduce brain damage following reperfusion. Clinical studies suggest a positive correlation between the increased influx of neutrophils and severity of brain injury following reperfusion. Integrin α9β1 is highly expressed on activated neutrophils and contributes to stable adhesion, but its role in stroke outcome has not been demonstrated to date.ObjectiveWe sought to determine the mechanistic role of myeloid-specific α9β1 in the progression of ischemic stroke in murine models with preexisting comorbidities.Methods and resultsWe generated novel myeloid-specific α9-deficient (α9-/-) wild type (α9fl/flLysMCre+/-), hyperlipidemic (α9fl/flLysMCre+/-Apoe-/-), and aged (bone marrow chimeric) mice to evaluate stroke outcome. Susceptibility to ischemia/reperfusion injury was evaluated at 1, 7, and 28 days following reperfusion in 2 models of experimental stroke: filament and embolic. We found that peripheral neutrophils displayed elevated α9 expression following stroke. Irrespective of sex, genetic deletion of α9 in myeloid cells improved short- and long-term stroke outcomes in the wild type, hyperlipidemic, and aged mice. Improved stroke outcome and enhanced survival in myeloid-specific α9-/- mice was because of marked decrease in cerebral thromboinflammatory response as evidenced by reduced fibrin, platelet thrombi, neutrophil, NETosis, and decreased phospho-NF-κB (nuclear factor-κB), TNF (tumor necrosis factor)-α, and IL (interleukin)-1β levels. α9-/- mice were less susceptible to FeCl3 injury-induced carotid artery thrombosis that was concomitant with improved regional cerebral blood flow following stroke as revealed by laser speckle imaging. Mechanistically, fibronectin containing extra domain A, a ligand for integrin α9, partially contributed to α9-mediated stroke exacerbation. Infusion of a specific anti-integrin α9 inhibitor into hyperlipidemic mice following reperfusion significantly reduced infarct volume and improved short- and long-term functional outcomes up to 28 days.ConclusionsWe provide genetic and pharmacological evidence for the first time that targeting myeloid-specific integrin α9β1 improves short- and long-term functional outcomes in stroke models with preexisting comorbidities by limiting cerebral thrombosis and inflammation.

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Dataset Information

Persistent inflammation worsens short-term outcomes in massive stroke patients.

Background

Methods

Conclusions

Publications

Persistent inflammation worsens short-term outcomes in massive stroke patients.

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