scholarly journals Impact of aging and comorbidities on ischemic stroke outcomes in preclinical animal models: A translational perspective

2021 ◽  
Vol 335 ◽  
pp. 113494
Author(s):  
Eduardo Candelario-Jalil ◽  
Surojit Paul
Keyword(s):  
Ischemic Stroke ◽  
Animal Models ◽  
Stroke Outcomes ◽  
Preclinical Animal Models

Preclinical and clinical evidence of IGF-1 as a prognostic marker and acute intervention with ischemic stroke

2021 ◽  
pp. 0271678X2110008
Author(s):  
Cellas A Hayes ◽  
M Noa Valcarcel-Ares ◽  
Nicole M Ashpole
Keyword(s):  
Ischemic Stroke ◽  
Animal Models ◽  
The Elderly ◽  
Clinical Settings ◽  
Mortality And Morbidity ◽  
Routes Of Administration ◽  
Insulin Growth Factor ◽  
Cellular Processes ◽  
Preclinical Animal Models

Ischemic strokes are highly prevalent in the elderly population and are a leading cause of mortality and morbidity worldwide. The risk of ischemic stroke increases in advanced age, corresponding with a noted decrease in circulating insulin growth factor-1 (IGF-1). IGF-1 is a known neuroprotectant involved in embryonic development, neurogenesis, neurotransmission, cognition, and lifespan. Clinically, several studies have shown that reduced levels of IGF-1 correlate with increased mortality rate, poorer functional outcomes, and increased morbidities following an ischemic stroke. In animal models of ischemia, administering exogenous IGF-1 using various routes of administration (intranasal, intravenous, subcutaneous, or topical) at various time points prior to and following insult attenuates neurological damage and accompanying behavioral changes caused by ischemia. However, there are some contrasting findings in select clinical and preclinical studies. This review discusses the role of IGF-1 as a determinant factor of ischemic stroke outcomes, both within the clinical settings and preclinical animal models. Furthermore, the review provides insight on the role of IGF-1 in mechanisms and cellular processes that contribute to stroke damage.

scholarly journals Increased P450 aromatase levels in post-menopausal women after acute ischemic stroke

2020 ◽  
Author(s):  
Bharti Manwani ◽  
Pamela Fall ◽  
Liang Zhu ◽  
Meaghan Roy O’Reilly ◽  
Sarah Conway ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Animal Models ◽  
Acute Stroke ◽  
Acute Ischemic Stroke ◽  
Sex Steroids ◽  
Aromatase Activity ◽  
Stroke Outcomes ◽  
Menopausal Women ◽  
Post Menopausal ◽  
Estradiol Levels

Abstract Background: Sex differences in stroke have been attributed to the neuroprotective effects of estrogen, yet most clinical trials of estrogen supplementation for stroke prevention have failed. The contribution of sex hormones to stroke outcome remains a subject of debate. Aromatization of testosterone to estradiol in neural tissue leads to sexual differentiation. Emerging data suggests aromatase activity increases in response to brain injury, and increased aromatase expression is seen in the ischemic penumbra in animal models. The objective of this study was to examine the levels of endogenous sex steroids after acute ischemic stroke and determine if levels of sex steroids were associated with acute stroke outcomes.Methods: Peripheral blood from ischemic stroke patients was collected under an approved IRB within 24 hours of symptom onset. 17 β estradiol, testosterone and aromatase levels were measured in the serum of both men and women. Hormone levels were compared in men vs. women in stroke and control groups and correlated with outcomes (NIHSS and change in the modified Rankin Scale (mRS), defined as difference of premorbid and discharge mRS) using multivariate regression.Results: We found no significant change in estradiol levels 24 hours after stroke in men (p = 0.86) or women (p = 0.10). In men, testosterone significantly decreased after stroke as compared with controls (1.83 ± 0.12 vs 2.86 ± 0.65, p = 0.01). Aromatase levels were significantly higher in women after stroke as compared with controls (2.27 ± 0.22 vs 0.97 ± 0.22, p = 0.002), but not in men (p = 0.84). Estradiol levels positively correlated with higher NIHSS at the time of admission, (r = 0.62, p = 0.0001) and higher change in mRS, (r = 0.38, p = 0.02) in women. Similar correlations between estradiol levels with NIHSS, (r = 0.34, p = 0.02) and change in mRS, r = 0.3, p = 0.04, was seen in men.Conclusions: Higher estradiol levels correlated with worse acute stroke outcomes, regardless of the sex. Testosterone levels decreased after stroke in men. As seen in animal models, aromatase levels increase after acute ischemic stroke, but this was only true for older women. These indicate an active aromatization process in post-menopausal women after acute ischemic stroke. We speculate that aromatase mediated local production of estradiol may occur in the female brain after acute ischemic stroke.

scholarly journals Comparison of Ischemic Stroke Outcomes and Patient and Hospital Characteristics by Race/Ethnicity and Socioeconomic Status

Stroke ◽  
2013 ◽  
Vol 44 (2) ◽  
pp. 469-476 ◽  
Author(s):  
Amresh D. Hanchate ◽  
Lee H. Schwamm ◽  
Wei Huang ◽  
Elaine M. Hylek
Keyword(s):  
Socioeconomic Status ◽  
Ischemic Stroke ◽  
Stroke Outcomes ◽  
Race Ethnicity ◽  
Hospital Characteristics

scholarly journals Impact of Comorbidities on Ischemic Stroke Outcomes in Women

Stroke ◽  
2008 ◽  
Vol 39 (7) ◽  
pp. 2138-2140 ◽  
Author(s):  
Cheryl D. Bushnell ◽  
Jeanne Lee ◽  
Pamela W. Duncan ◽  
L. Kristin Newby ◽  
Larry B. Goldstein
Keyword(s):  
Ischemic Stroke ◽  
Stroke Outcomes

scholarly journals Dysphagia in Patients with Acute Ischemic Stroke: Early Dysphagia Screening May Reduce Stroke-Related Pneumonia and Improve Stroke Outcomes

2016 ◽  
Vol 42 (1-2) ◽  
pp. 81-89 ◽  
Author(s):  
Mohamed Al-Khaled ◽  
Christine Matthis ◽  
Andreas Binder ◽  
Jonas Mudter ◽  
Joern Schattschneider ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Case Fatality ◽  
National Institutes Of Health ◽  
Modified Rankin Scale ◽  
Stroke Patients ◽  
Stroke Outcomes ◽  
Increased Risk ◽  
Reduced Risk

Background: Dysphagia is associated with poor outcome in stroke patients. Studies investigating the association of dysphagia and early dysphagia screening (EDS) with outcomes in patients with acute ischemic stroke (AIS) are rare. The aims of our study are to investigate the association of dysphagia and EDS within 24 h with stroke-related pneumonia and outcomes. Methods: Over a 4.5-year period (starting November 2007), all consecutive AIS patients from 15 hospitals in Schleswig-Holstein, Germany, were prospectively evaluated. The primary outcomes were stroke-related pneumonia during hospitalization, mortality, and disability measured on the modified Rankin Scale ≥2-5, in which 2 indicates an independence/slight disability to 5 severe disability. Results: Of 12,276 patients (mean age 73 ± 13; 49% women), 9,164 patients (74%) underwent dysphagia screening; of these patients, 55, 39, 4.7, and 1.5% of patients had been screened for dysphagia within 3, 3 to <24, 24 to ≤72, and >72 h following admission. Patients who underwent dysphagia screening were likely to be older, more affected on the National Institutes of Health Stroke Scale score, and to have higher rates of neurological symptoms and risk factors than patients who were not screened. A total of 3,083 patients (25.1%; 95% CI 24.4-25.8) had dysphagia. The frequency of dysphagia was higher in patients who had undergone dysphagia screening than in those who had not (30 vs. 11.1%; p < 0.001). During hospitalization (mean 9 days), 1,271 patients (10.2%; 95% CI 9.7-10.8) suffered from stroke-related pneumonia. Patients with dysphagia had a higher rate of pneumonia than those without dysphagia (29.7 vs. 3.7%; p < 0.001). Logistic regression revealed that dysphagia was associated with increased risk of stroke-related pneumonia (OR 3.4; 95% CI 2.8-4.2; p < 0.001), case fatality during hospitalization (OR 2.8; 95% CI 2.1-3.7; p < 0.001) and disability at discharge (OR 2.0; 95% CI 1.6-2.3; p < 0.001). EDS within 24 h of admission appeared to be associated with decreased risk of stroke-related pneumonia (OR 0.68; 95% CI 0.52-0.89; p = 0.006) and disability at discharge (OR 0.60; 95% CI 0.46-0.77; p < 0.001). Furthermore, dysphagia was independently correlated with an increase in mortality (OR 3.2; 95% CI 2.4-4.2; p < 0.001) and disability (OR 2.3; 95% CI 1.8-3.0; p < 0.001) at 3 months after stroke. The rate of 3-month disability was lower in patients who had received EDS (52 vs. 40.7%; p = 0.003), albeit an association in the logistic regression was not found (OR 0.78; 95% CI 0.51-1.2; p = 0.2). Conclusions: Dysphagia exposes stroke patients to a higher risk of pneumonia, disability, and death, whereas an EDS seems to be associated with reduced risk of stroke-related pneumonia and disability.

Abstract MP16: Excessive White Matter Hyperintensity Burden and Functional Outcomes After Acute Ischemic Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Sungmin Hong ◽  
Anne-katrin Giese ◽  
Markus D Schirmer ◽  
Adrian V Dalca ◽  
Anna Bonkhoff ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Ischemic Stroke ◽  
Functional Outcomes ◽  
Life Time ◽  
Stroke Recovery ◽  
White Matter Hyperintensity ◽  
Brain Health ◽  
Stroke Outcomes ◽  
The Brain

Objective: Ability of the brain to recover after an acute ischemic stroke (AIS) is linked to the pre-stroke burden of white matter hyperintensity (WMH), a radiographic marker of brain health. We sought to determine the excessive WMH burden in an AIS population and investigate its association with 3-month stroke outcomes. Data: We used 2,435 subjects from the MRI-GENIE study. Three-month functional outcomes of 872 subjects among those subjects were measured by 90-day modified Ranking Scale (mRS). Methods: We automatically quantified WMH volume (WMHv) on FLAIR images and adjusted for a brain volume. We modeled a trend using the factor analysis (FA) log-linear regression using age, sex, atrial fibrillation, diabetes, hypertension, coronary artery disease and smoking as input variables. We categorized three WMH burden groups based on the conditional probability given by the model (LOW: lower 33%, MED: middle 34%, and HIGH: upper 33%). The subgroups were compared with respect to mRS (median and dichotomized odds ratio (OR) (good/poor: mRS 0-2/3-6)). Results: Five FA components out of seven with significant relationship to WMHv (p<0.001) were used for the regression modeling (R 2 =0.359). The HIGH group showed higher median (median=2, IQR=2) mRS score than LOW (median=1, IQR=1) and MED (median=1, IQR=1). The odds (OR) of good AIS outcome for LOW and MED were 1.8 (p=0.0001) and 1.6 (p=0.006) times higher than HIGH, respectively. Conclusion: Once accounted for clinical covariates, the excessive WMHv was associated with worse 3-month stroke outcomes. These data suggest that a life-time of injury to the white matter reflected in WMH is an important factor for stroke recovery and an indicator of the brain health.

scholarly journals Different Strokes for Different Folks: The Rich Diversity of Animal Models of Focal Cerebral Ischemia

2010 ◽  
Vol 30 (8) ◽  
pp. 1412-1431 ◽  
Author(s):  
David W Howells ◽  
Michelle J Porritt ◽  
Sarah SJ Rewell ◽  
Victoria O'Collins ◽  
Emily S Sena ◽  
...  
Keyword(s):  
Animal Model ◽  
Ischemic Stroke ◽  
Animal Models ◽  
Focal Cerebral Ischemia ◽  
Experimental Stroke ◽  
Stroke Outcome ◽  
Rich Diversity ◽  
Single Animal ◽  
The Rich ◽  
Use Of Models

No single animal model is able to encompass all of the variables known to affect human ischemic stroke. This review highlights the major strengths and weaknesses of the most commonly used animal models of acute ischemic stroke in the context of matching model and experimental aim. Particular emphasis is placed on the relationships between outcome and underlying vascular variability, physiologic control, and use of models of comorbidity. The aim is to provide, for novice and expert alike, an overview of the key controllable determinants of experimental stroke outcome to help ensure the most effective application of animal models to translational research.

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