Ischemic-time associated reductions in equol monosulfate plasma levels in a mouse model of ischemic stroke: support the existence of a ‘brain–gut axis’

Introduction: Plasma concentrations of prothrombotic factors such as fibrinogen have previously been associated with ischemic stroke risk. To extend this observation, we examined the association of polygenic risk scores (PRS) for increased plasma levels of thrombosis-related factors with ischemic stroke. Our hypotheses were that these PRS would be more associated with early than late onset stroke and with non-lacunar than lacunar stroke. Methods: We identified 9053 late onset (≥ 60 years) stroke cases from the NINDS International Stroke Genetics Consortium (SiGN) with 24804 controls and 6594 early onset (< 60 years) stroke cases from the Genetics of Early Onset Ischemic Stroke Consortium with 30561 controls. We identified previously known loci associated with plasma levels of four thrombosis-related factors: fibrinogen, fibrin D-dimer, tPA and PAI-1 from prior GWAS studies and developed genome-wide PRS for plasma concentrations of these factors. We then used logistic regression to test the association of these scores with risk of stroke and stroke subtype. Results: PRS for fibrin D dimer levels were associated with increased risk for all stroke and specifically for older (p = 0.019), but not younger (p = 0.22) onset stroke. PRS for tPA levels were also marginally associated with older (p = 0.06), but not younger (p = 0.24) onset stroke. Genetic risk scores for both D dimer and tPA were associated with non-lacunar stroke (Table 1). Further analyses stratified by age revealed PRS for D dimer to be significantly associated with non-lacunar stroke (but not lacunar stroke) in both late and early onset cohorts. PRS for fibrinogen and PAI-1 were not associated with stroke. Conclusion: Genomic risk scores for thrombosis-related factors including D dimer and tPA levels were associated with risk for ischemic stroke, and specifically, non-lacunar stroke.

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Notch3 Mutation Detection in Stroke Patients and Selective Nanoliposome in Stroke Alleviation in a Mouse Model

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2021.3142 ◽

2021 ◽

Vol 17 (9) ◽

pp. 1735-1744

Author(s):

Yanxia Wang ◽

Xinmeng Li ◽

Ying Liu ◽

Wenjing Guo ◽

Jiangpo Chen ◽

...

Keyword(s):

Ischemic Stroke ◽

Mouse Model ◽

Control Group ◽

Stroke Therapy ◽

Stroke Patients ◽

Brain Vessels ◽

Stroke Treatment ◽

Pathological Alteration ◽

Notch3 Mutation ◽

Long Term Prognosis

This study analyzed the correlation between the Notch3 mutation and stroke by testing an effective nanoparticle-loaded aspirin in stroke therapy. Fifty patients with ischemic stroke were followed for two years, and fifty healthy persons served as the control group. By RT-PCR, this study revealed that the Notch3 mutation existed in ischemic stroke patients who were more likely to have a family history, small vessel lesions, relatively frequent cerebral hemorrhage, and poor long-term prognosis. Liposome-aspirin-chitosan nanoparticle (LACN) was constructed as a nano-composite for stroke treatment. Notch3 Arg170Cys knock-in mice were prepared as a mutant Notch3 mouse model to test the LACN infiltration efficiency and observe the anti-stroke capacity. We found that LACN could better transport aspirin into brain vessels than the Polyethyleneimine (PEI) delivery system. However, in the Notch3 mutation mouse model, cerebral infarction and hemorrhage often occurred after being treated with aspirin. Still, LACN better prolongs the half-life of aspirin, rescues the pathological alteration of stroke in the brain, and reduces inflammatory reaction and oxidative stress response. In conclusion, the Notch3 mutation is closely related to stroke occurrence, and LACN may be a better choice for stroke therapy in the future.

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Sex-Related Differences in Management and Outcome of Acute Ischemic Stroke in Eligible Patients to Thrombolysis

Cerebrovascular Diseases ◽

10.1159/000500901 ◽

2019 ◽

Vol 47 (3-4) ◽

pp. 196-204 ◽

Cited By ~ 2

Author(s):

Laurie Fraticelli ◽

Julie Freyssenge ◽

Clément Claustre ◽

Marielle Buisson ◽

Magali Bischoff ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Urban Landscape ◽

Real Life ◽

Rural Landscape ◽

Response To Treatment ◽

Ischemic Time ◽

Intravenous Tissue Plasminogen Activator ◽

Prehospital Management

Background: Literature has highlighted sex-based differences in the natural course of stroke and in response to treatment with intravenous tissue plasminogen activator (tPA). Objectives: We aimed to compare the management and outcome of acute ischemic stroke (AIS) among women and men on a French registry based on a federated network of emergency physicians and neurologists. Method: We included 2,790 patients received tPA between 2010 and 2016 from the stroke centers in the RESUVal area. We provided age-adjusted analysis and multivariate models for determining the role of sex in the outcome measures. Results: After age-adjustment, women presented more moderate to severe stroke at admission with more proximal occlusions. Among tPA eligible patients, the therapeutic strategy and in-hospital hemorrhagic complications were proportionally identical whatever the sex. The total ischemic time from onset symptom to thrombolysis did not differ from women to men. Age-adjusted 3-month mortality did not differ between women and men, and the determinants of mortality were age (relative risk [RR] 1.56 [1.37–1.78], p < 0.0001), proximal occlusion (RR 2.5 [1.88–3.33], p < 0.0001), and at least one complication (RR 2.43 [1.89–3.13], p < 0.0001). The determinants of poor functional outcome at 3 months were the sex (RR 1.22 [1.01–1.48] for women, p = 0.0385) and the occurrence of onset symptom in rural landscape (RR 1.26 [1.03–1.55], p = 0.0219) compared to urban landscape. Conclusions: We provided an exhaustive overview and real-life professional practices conditions in thrombolyzed AIS. Despite a later prehospital management in neurovascular units and more severe strokes at admission, women and men had both similar outcomes at hospital discharge and in 3-month survival, but women were associated to worst functional outcome at 3 months.

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