Lack of lymphocytes exacerbate heat stroke severity in male mice through enhanced inflammatory response

Abstract Background The occurrence of systemic inflammatory response syndrome (SIRS) is associated with poor outcomes after ischemic stroke, and the inflammatory response can be significantly attenuated by successful reperfusion, while the SIRS in patients with acute large vessel occlusion stroke (ALVOS) who underwent endovascular treatment (EVT) remain unclear. We aimed to investigate the occurrence rate, predictors, and clinical outcomes of SIRS in patients with ALVOS after EVT. Methods We retrospectively collected EVT data of patients with ALVOS from July 2014 to August 2019 in our center. SIRS in the absence of infection was defined as the presence of ≥2 of the following: (1) heart rate >90 (2) body temperature >38°C or <36°C, (3) white blood cells >12 000/mm or <4000/mm or >10% bands for >24 h or (4) respiratory rate >20. Favorable outcome was defined as obtaining a 90-day modified Rankin Scale (mRS) score ≤2. Results Among the 262 patients who received EVT, 92 (35.1%) developed SIRS, 88 (95.7%) of whom developed SIRS in the first two days after EVT. Patients who developed SIRS had a reduced favorable outcome (OR, 4.112 [95% CI, 1.705–9.920]; P=0.002) and higher mortality (OR, 25.236 [95% CI, 8.578–74.835]; P<0.001) at 90 days. Greater SIRS burden was positively correlated with NIHSS scores at discharge and mRS scores at 90 days (r=0.249, P=0.017; r=0.230, P=0.027). The development of SIRS in patients with ALOVS who underwent EVT was associated with neutrophilic leukocytosis, hyperglycemia, higher admission NIHSS scores, and worse collateral circulation. Conclusions Patients with SIRS had higher odds of poor functional outcomes and higher mortality at 90 days in the EVT-treatment setting. The severity of the inflammatory response was positively correlated with the clinical outcomes of patients. Clinically relevant associations with SIRS were neutrophilic leukocytosis, hyperglycemia and baseline stroke severity, but favorable collateral circulation was a protective factor against SIRS.

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Treatment with Edoxaban Attenuates Acute Stroke Severity in Mice by Reducing Blood–Brain Barrier Damage and Inflammation

International Journal of Molecular Sciences ◽

10.3390/ijms22189893 ◽

2021 ◽

Vol 22 (18) ◽

pp. 9893

Author(s):

Michael Bieber ◽

Kathrin I. Foerster ◽

Walter E. Haefeli ◽

Mirko Pham ◽

Michael K. Schuhmann ◽

...

Keyword(s):

Inflammatory Response ◽

Blood Brain Barrier ◽

Focal Cerebral Ischemia ◽

Ischemia Reperfusion ◽

Brain Barrier ◽

Protective Mechanism ◽

Stroke Severity ◽

Local Inflammatory Response ◽

Blood Brain ◽

Increased Risk

Patients with atrial fibrillation and previous ischemic stroke (IS) are at increased risk of cerebrovascular events despite anticoagulation. In these patients, treatment with non-vitamin K oral anticoagulants (NOAC) such as edoxaban reduced the probability and severity of further IS without increasing the risk of major bleeding. However, the detailed protective mechanism of edoxaban has not yet been investigated in a model of ischemia/reperfusion injury. Therefore, in the current study we aimed to assess in a clinically relevant setting whether treatment with edoxaban attenuates stroke severity, and whether edoxaban has an impact on the local cerebral inflammatory response and blood–brain barrier (BBB) function after experimental IS in mice. Focal cerebral ischemia was induced by transient middle cerebral artery occlusion in male mice receiving edoxaban, phenprocoumon or vehicle. Infarct volumes, functional outcome and the occurrence of intracerebral hemorrhage were assessed. BBB damage and the extent of local inflammatory response were determined. Treatment with edoxaban significantly reduced infarct volumes and improved neurological outcome and BBB function on day 1 and attenuated brain tissue inflammation. In summary, our study provides evidence that edoxaban might exert its protective effect in human IS by modulating different key steps of IS pathophysiology, but further studies are warranted.

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Pertussis Toxin Induced Inflammatory Response Exacerbates Intracerebral Hemorrhage and Ischemic Stroke in Mice

10.21203/rs.3.rs-126762/v1 ◽

2020 ◽

Author(s):

Ming Zou ◽

Yan Li ◽

Hui Zhao ◽

Yan Feng ◽

Ying Zhang ◽

...

Keyword(s):

Ischemic Stroke ◽

Inflammatory Response ◽

Mouse Model ◽

Intracerebral Hemorrhage ◽

Blood Brain Barrier ◽

Pertussis Toxin ◽

Brain Inflammation ◽

Brain Barrier ◽

Stroke Severity ◽

Blood Brain

Abstract Background: Stroke is a devastating and debilitating disease and is a leading cause of death worldwide, including intracerebral hemorrhage (ICH) and ischemic stroke. Emerging evidence indicates that inflammatory cascades after hemorrhagic or ischemic stroke makes a great contribution to brain damage, mainly are involved in neuronal cell death, blood-brain-barrier (BBB) destruction and development of vasogenic edema. However, the features and direct effect of brain inflammation following stroke is still unknown. Methods: We adopted the ICH model by injection of collagenase and used a mouse model of transient cerebral ischemia and reperfusion. And pertussis toxin was used to create a pro-inflammatory milieu. Neurodeficits, lesion volume, production of reactive oxygen species (ROS) and inflammatory factors, brain-infiltrating leukocytes and blood-brain-barrier (BBB) destruction were assessed in mice model treated with pertussis toxin or vehicle.Results: Adopting collagenase induced intracerebral hemorrhage mouse model, we show that pertussis toxin-induced systemic inflammation exacerbated neurological deficits, enlarged lesion size and brain perihematomal edema after intracerebral hemorrhage. Pertussis toxin promoted leukocyte infiltration and inflammatory cytokine release in the brain. Moreover, the integrity of the BBB was further disrupted after receiving pertussis toxin in ICH mice. Furthermore, we demonstrated that pertussis toxin increased stroke severity and enhanced brain inflammation in middle cerebral artery occlusion (MCAO) mouse model. Conclusion: Our results suggest that pertussis toxin increases inflammatory response that exacerbates brain injury after intracerebral hemorrhage or ischemic stroke in mouse model.

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Myocardial oxidative stress and inflammation emerges during recovery from exertional heat stroke in female but not male mice

The FASEB Journal ◽

10.1096/fasebj.2020.34.s1.03584 ◽

2020 ◽

Vol 34 (S1) ◽

pp. 1-1

Author(s):

Christian K. Garcia ◽

Gerard P. Robinson ◽

Alex J. Mattingly ◽

John D. Iwaniec ◽

Lucas De Carvalho ◽

...

Keyword(s):

Oxidative Stress ◽

Heat Stroke ◽

Male Mice ◽

Exertional Heat Stroke ◽

Myocardial Oxidative Stress

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Systemic Inflammatory Response Depends on Initial Stroke Severity but Is Attenuated by Successful Thrombolysis

Stroke ◽

10.1161/01.str.0000152951.14573.f8 ◽

2005 ◽

Vol 36 (2) ◽

pp. 232-232 ◽

Cited By ~ 2

Author(s):

Kerstin Sander ◽

Dirk Sander

Keyword(s):

Inflammatory Response ◽

Systemic Inflammatory Response ◽

Stroke Severity ◽

Successful Thrombolysis

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Chickpea supplementation prior to colitis onset reduces inflammation in dextran sodium sulfate-treated C57Bl/6 male mice

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2017-0689 ◽

2018 ◽

Vol 43 (9) ◽

pp. 893-901 ◽

Cited By ~ 4

Author(s):

Jennifer M. Monk ◽

Wenqing Wu ◽

Laurel H. McGillis ◽

Hannah R. Wellings ◽

Amber L. Hutchinson ◽

...

Keyword(s):

Inflammatory Response ◽

Sodium Sulfate ◽

Clinical Symptoms ◽

Basal Diet ◽

Serum Levels ◽

Dextran Sodium Sulfate ◽

Male Mice ◽

Acute Colitis ◽

Colon Tissue ◽

Necrosis Factor Alpha

The potential for a chickpea-supplemented diet (rich in fermentable nondigestible carbohydrates and phenolic compounds) to modify the colonic microenvironment and attenuate the severity of acute colonic inflammation was investigated. C57Bl/6 male mice were fed a control basal diet or basal diet supplemented with 20% cooked chickpea flour for 3 weeks prior to acute colitis onset induced by 7-day exposure to dextran sodium sulfate (DSS; 2% w/v in drinking water) and colon and serum levels of inflammatory mediators were assessed. Despite an equal degree of DSS-induced epithelial barrier histological damage and clinical symptoms between dietary groups, biomarkers of the ensuing inflammatory response were attenuated by chickpea pre-feeding, including reduced colon tissue activation of nuclear factor kappa B and inflammatory cytokine production (tumor necrosis factor alpha and interleukin (IL)-18). Additionally, colon protein expression of anti-inflammatory (IL-10) and epithelial repair (IL-22 and IL-27) cytokines were increased by chickpea pre-feeding. Furthermore, during acute colitis, chickpea pre-feeding increased markers of enhanced colonic function, including Relmβ and IgA gene expression. Collectively, chickpea pre-feeding modulated the baseline function of the colonic microenvironment, whereby upon induction of acute colitis, the severity of the inflammatory response was attenuated.

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