Sex Differences, Progesterone, and Ischemic Stroke

2019 ◽  
pp. 209-231
Author(s):  
Michael Schumacher ◽  
Rachida Guennoun
Keyword(s):  
Sex Differences ◽  
Ischemic Stroke

Abstract TP274: Orosomucoid-1 Protein Increases Following Ischemic Stroke in the Brain and Periphery

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Hetal Mistry ◽  
Madeline Levy ◽  
Meaghan Roy-O'Reilly ◽  
Louise McCullough
Keyword(s):  
Sex Differences ◽  
Ischemic Stroke ◽  
Rna Sequencing ◽  
Multiple Testing ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Stroke Patients ◽  
Post Stroke ◽  
Protein Levels ◽  
The Brain

Background and Purpose: Orosomucoid-1 (ORM-1) is an abundant protein with important roles in inflammation and immunosuppression. We utilized RNA sequencing to measure mRNA levels in human ischemic stroke patients, with confirmation by serum ORM-1 protein measurements. A mouse model of ischemic stroke was then used to examine post-stroke changes in ORM-1 within the brain itself. Hypothesis: We tested the hypothesis that ORM-1 levels increase following ischemic stroke, with sex differences in protein dynamics over time. Methods: RNA sequencing was performed on whole blood from ischemic stroke patients (n=23) and controls (n=12), with Benjamini-Hochberg correction for multiple testing. Enzyme-linked immunosorbent assay was performed on serum from ischemic stroke patients (n=28) and controls (n=8), with analysis by T-test. For brain analysis, mice (n=14) were subjected to a 90-minute middle cerebral artery occlusion (MCAO) surgery and sacrificed 6 or 24 hours after stroke. Control mice underwent parallel “sham” surgery without occlusion. Western blotting was used to detect ORM-1 protein levels in whole brain, with analysis by two-way ANOVA. Results: RNA sequencing showed a 2.8-fold increase in human ORM-1 at 24 hours post-stroke (q=.0029), an increase also seen in serum ORM-1 protein levels (p=.011). Western blot analysis of mouse brain revealed that glycosylated (p=0.0003) and naive (p=0.0333) forms of ORM-1 were higher in female mice compared to males 6 hours post-stroke. Interestingly, ORM-1 levels were higher in the brains of stroke mice at 6 hours (p=.0483), while at 24 hours ORM-1 levels in stroke mice were lower than their sham counterparts (p=.0212). In both human and mouse data, no sex differences were seen in ORM-1 levels in the brain or periphery at 24 hours post-stroke. Conclusion: In conclusion, ORM-1 is a sexually dimorphic protein involved in the early (<24 hour) response to ischemic stroke. This research serves as an initial step in determining the mechanism of ORM-1 in the ischemic stroke response and its potential as a future therapeutic target for both sexes.

scholarly journals Sex Differences in Ischemic Stroke Outcomes in Patients With Pulmonary Hypertension

2021 ◽  
Author(s):  
Tiberiu A. Pana ◽  
Dana K. Dawson ◽  
Mohamed O. Mohamed ◽  
Fiona Murray ◽  
David L. Fischman ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Sex Differences ◽  
Ischemic Stroke ◽  
Hospital Mortality ◽  
Acute Ischemic Stroke ◽  
Systemic Hypertension ◽  
Stroke Outcomes ◽  
Female Patients ◽  
Prolonged Hospitalization ◽  
The Impact

Background The association between systemic hypertension and cerebrovascular disease is well documented. However, the impact of pulmonary hypertension (PH) on acute ischemic stroke outcomes is unknown despite PH being recognized as a risk factor for acute ischemic stroke. We aimed to determine the association between PH and adverse in‐hospital outcomes after acute ischemic stroke, as well as whether there are sex differences in this association. Methods and Results Acute ischemic stroke admissions from the US National Inpatient Sample between October 2015 and December 2017 were included. The relationship between PH and outcomes (mortality, prolonged hospitalization >4 days, and routine home discharge) was analyzed using logistic regressions adjusting for demographics, comorbidities, and revascularization therapies. Interaction terms between PH and sex and age groups were also included. A total of 221 249 records representative of 1 106 045 admissions were included; 2.9% of patients had co‐morbid PH, and 35.34% of those were male. PH was not associated with in‐hospital mortality (odds ratio [OR], 0.96; 95% CI, 0.86–1.09) but was associated with increased odds of prolonged hospitalization (OR, 1.15; 95% CI, 1.09–1.22) and decreased odds of routine discharge (OR, 0.87; 95% CI, 0.81–0.94) for both sexes. Older patients with PH were significantly less likely to be discharged routinely ( P =0.028) than their younger counterparts. Compared with female patients with PH, men were 31% more likely to die in hospital ( P =0.024). Conclusions PH was not significantly associated with in‐hospital mortality but was associated with prolonged hospitalization and adverse discharge status. Male patients with PH were more likely to die in hospital than female patients.

scholarly journals Sex Differences in the Impact of Shift Work Schedules on Pathological Outcomes in an Animal Model of Ischemic Stroke

Endocrinology ◽  
2016 ◽  
Vol 157 (7) ◽  
pp. 2836-2843 ◽  
Author(s):  
David J. Earnest ◽  
Nichole Neuendorff ◽  
Jason Coffman ◽  
Amutha Selvamani ◽  
Farida Sohrabji
Keyword(s):  
Animal Model ◽  
Sex Differences ◽  
Ischemic Stroke ◽  
Shift Work ◽  
Work Schedules ◽  
The Impact

Abstract TP233: Sex Differences in30-DayReadmission Rates After Ischemic Stroke - A Nationwide Study

Stroke ◽  
2019 ◽  
Vol 50 (Suppl_1) ◽  
Author(s):  
Ashley Wabnitz ◽  
Alain Lekoubou Looti ◽  
Kinfe Bishu ◽  
Bruce Ovbiagele
Keyword(s):  
Sex Differences ◽  
Ischemic Stroke ◽  
Nationwide Study

scholarly journals Sex Differences in Ischemic Stroke Sensitivity Are Influenced by Gonadal Hormones, Not by Sex Chromosome Complement

2014 ◽  
Vol 35 (2) ◽  
pp. 221-229 ◽  
Author(s):  
Bharti Manwani ◽  
Kathryn Bentivegna ◽  
Sharon E Benashski ◽  
Venugopal Reddy Venna ◽  
Yan Xu ◽  
...  
Keyword(s):  
Sex Differences ◽  
Ischemic Stroke ◽  
Sex Hormones ◽  
Sex Chromosome ◽  
Chromosome Complement ◽  
Serum Testosterone ◽  
Gonadal Hormones ◽  
Epidemiologic Studies ◽  
Artery Occlusion ◽  
Male Mice

Epidemiologic studies have shown sex differences in ischemic stroke. The four core genotype (FCG) mouse model, in which the testes determining gene, Sry, has been moved from Y chromosome to an autosome, was used to dissociate the effects of sex hormones from sex chromosome in ischemic stroke outcome. Middle cerebral artery occlusion (MCAO) in gonad intact FCG mice revealed that gonadal males (XXM and XYM) had significantly higher infarct volumes as compared with gonadal females (XXF and XYF). Serum testosterone levels were equivalent in adult XXM and XYM, as was serum estrogen in XXF and XYF mice. To remove the effects of gonadal hormones, gonadectomized FCG mice were subjected to MCAO. Gonadectomy significantly increased infarct volumes in females, while no change was seen in gonadectomized males, indicating that estrogen loss increases ischemic sensitivity. Estradiol supplementation in gonadectomized FCG mice rescued this phenotype. Interestingly, FCG male mice were less sensitive to effects of hormones. This may be due to enhanced expression of the transgene Sry in brains of FCG male mice. Sex differences in ischemic stroke sensitivity appear to be shaped by organizational and activational effects of sex hormones, rather than sex chromosomal complement.

scholarly journals Sex differences in T cell immune responses, gut permeability and outcome after ischemic stroke in aged mice

2020 ◽  
Vol 87 ◽  
pp. 556-567 ◽  
Author(s):  
Hilda Ahnstedt ◽  
Anthony Patrizz ◽  
Anjali Chauhan ◽  
Meaghan Roy-O'Reilly ◽  
Joseph W. Furr ◽  
...  
Keyword(s):  
Sex Differences ◽  
Ischemic Stroke ◽  
T Cell ◽  
Immune Responses ◽  
Gut Permeability ◽  
Aged Mice ◽  
T Cell Immune Responses

scholarly journals First-Ever Ischemic Stroke and Incident Major Adverse Cardiovascular Events in 93 627 Older Women and Men

Stroke ◽  
2020 ◽  
Vol 51 (2) ◽  
pp. 387-394 ◽  
Author(s):  
Luciano A. Sposato ◽  
Melody Lam ◽  
Britney Allen ◽  
Salimah Z. Shariff ◽  
Gustavo Saposnik ◽  
...  
Keyword(s):  
Sex Differences ◽  
Heart Disease ◽  
Ischemic Stroke ◽  
Cardiovascular Events ◽  
Population Based ◽  
Major Adverse Cardiovascular Events ◽  
Cardiac Complications ◽  
Coronary Syndrome ◽  
Cardiovascular Comorbidities ◽  
Increased Risk

Background and Purpose— Stroke risk is sex-specific, but little is known about sex differences of poststroke major adverse cardiovascular events (MACEs). Stroke-related brain damage causes autonomic dysfunction and inflammation, sometimes resulting in cardiac complications. Sex-specific cardiovascular susceptibility to stroke without the confounding effect of preexisting heart disease constitutes an unexplored field because previous studies focusing on sex differences in poststroke MACE have not excluded patients with known cardiovascular comorbidities. We therefore investigated sex-specific risks of incident MACE in a heart disease-free population-based cohort of patients with first-ever ischemic stroke and propensity-matched individuals without stroke. Methods— We included Ontario residents ≥66 years, without known cardiovascular comorbidities, with first-ever ischemic stroke between 2002 and 2012 and propensity-matched individuals without stroke. We investigated the 1-year risk of incident MACE (acute coronary syndrome, myocardial infarction, incident coronary artery disease, coronary revascularization procedures, incident heart failure, or cardiovascular death) separately for females and males. For estimating cause-specific adjusted hazard ratios, we adjusted Cox models for variables with weighted standardized differences >0.10 or those known to influence MACE risk. Results— We included 93 627 subjects without known cardiovascular comorbidities; 21 931 with first-ever ischemic stroke and 71 696 propensity-matched subjects without stroke. Groups were well-balanced on propensity-matching variables. There were 53 476 women (12 421 with and 41 055 without ischemic stroke) and 40 151 men (9510 with and 30 641 without ischemic stroke). First-ever ischemic stroke was associated with increased risk of incident MACE in both sexes. The risk was time-dependent, highest within 30 days (women: adjusted hazard ratio, 25.1 [95% CI, 19.3–32.6]; men: aHR, 23.4 [95% CI, 17.2–31.9]) and decreasing but remaining significant between 31 and 90 days (women: aHR, 4.8 [95% CI, 3.8–6.0]; men: aHR, 4.2 [95% CI, 3.3–5.4]), and 91 to 365 days (aHR, 2.1 [95% CI, 1.8–2.3]; men: aHR, 2.0 [95% CI, 1.7–2.3]). Conclusions— In this large population-based study, ischemic stroke was independently associated with increased risk of incident MACE in both sexes.

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