scholarly journals Sex-Dependent Effects of Bmal1-Deficiency on Mouse Cerebral Cortex Infarction in Response to Photothrombotic Stroke

2018 ◽  
Vol 19 (10) ◽  
pp. 3124 ◽  
Author(s):  
Anne Lembach ◽  
Anna Stahr ◽  
Amira A. H. Ali ◽  
Marc Ingenwerth ◽  
Charlotte von Gall

Stroke is a leading cause of disability and death worldwide. There is increasing evidence that occurrence of ischemic stroke is affected by circadian system and sex. However, little is known about the effect of these factors on structural recovery after ischemic stroke. Therefore, we studied infarction in cerebral neocortex of male and female mice with deletion of the clock gene Bmal1 (Bmal1−/−) after focal ischemia induced by photothrombosis (PT). The infarct core size was significantly smaller 14 days (d) as compared to seven days after PT, consistent with structural recovery during the sub-acute phase. However, when sexes were analyzed separately 14 days after PT, infarct core was significantly larger in wild-type (Bmal1+/+) female as compared to male Bmal1+/+ mice, and in female Bmal1+/+, as compared to female Bmal1−/− mice. Volumes of reactive astrogliosis and densely packed microglia closely mirrored the size of infarct core in respective groups. Estradiol levels were significantly higher in female Bmal1−/− as compared to Bmal1+/+ mice. Our data suggests a sex-dependent effect and an interaction between sex and genotype on infarct size, the recruitment of astrocytes and microglia, and a relationship of these cells with structural recovery probably due to positive effects of estradiol during the subacute phase.

2020 ◽  
pp. 028418512098177
Author(s):  
Yu Lin ◽  
Nannan Kang ◽  
Jianghe Kang ◽  
Shaomao Lv ◽  
Jinan Wang

Background Color-coded multiphase computed tomography angiography (mCTA) can provide time-variant blood flow information of collateral circulation for acute ischemic stroke (AIS). Purpose To compare the predictive values of color-coded mCTA, conventional mCTA, and CT perfusion (CTP) for the clinical outcomes of patients with AIS. Material and Methods Consecutive patients with anterior circulation AIS were retrospectively reviewed at our center. Baseline collateral scores of color-coded mCTA and conventional mCTA were assessed by a 6-point scale. The reliabilities between junior and senior observers were assessed by weighted Kappa coefficients. Receiver operating characteristic (ROC) curves and multivariate logistic regression model were applied to evaluate the predictive capabilities of color-coded mCTA and conventional mCTA scores, and CTP parameters (hypoperfusion and infarct core volume) for a favorable outcome of AIS. Results A total of 138 patients (including 70 cases of good outcomes) were included in our study. Patients with favorable prognoses were correlated with better collateral circulations on both color-coded and conventional mCTA, and smaller hypoperfusion and infarct core volume (all P < 0.05) on CTP. ROC curves revealed no significant difference between the predictive capability of color-coded and conventional mCTA ( P = 0.427). The predictive value of CTP parameters tended to be inferior to that of color-coded mCTA score (all P < 0.001). Both junior and senior observers had consistently excellent performances (κ = 0.89) when analyzing color-coded mCTA maps. Conclusion Color-coded mCTA provides prognostic information of patients with AIS equivalent to or better than that of conventional mCTA and CTP. Junior radiologists can reach high diagnostic accuracy when interpreting color-coded mCTA images.


2006 ◽  
Vol 25 (4) ◽  
pp. 227-236
Author(s):  
Li-Fen Liao

Sharing knowledge and firm innovation are the crucial ways to sustain competitive advantage. This study builds a nested model to test the relationship between learning organization, knowledge-sharing behavior, and firm innovation. Data gathered from 254 employees were used to examine the relationship of the learning organization to employees' knowledge-sharing behavior and firm innovation. The results indicate that open-mindedness, shared vision and trust have positive effects on both knowledge-sharing behavior and firm innovation. While commitment to learning does not shows significant relationship on knowledge-sharing behavior and firm innovation. Communication has significance on firm innovation but not significance on knowledge-sharing behavior.


Author(s):  
Elisabeth Kliem ◽  
Elise Gjestad ◽  
Truls Ryum ◽  
Alexander Olsen ◽  
Bente Thommessen ◽  
...  

Abstract Objective: Findings on the relationship of psychiatric symptoms with performance-based and self-reported cognitive function post-stroke are inconclusive. We aimed to (1) study the relation of depression and anxiety to performance-based cognitive function and (2) explore a broader spectrum of psychiatric symptoms and their association with performance-based versus self-reported cognitive function. Method: Individuals with supratentorial ischemic stroke performed neuropsychological examination 3 months after stroke. For primary analyses, composite scores for memory and attention/executive function were calculated based on selected neuropsychological tests, and the Hospital Anxiety and Depression Scale (HADS) was used. Psychiatric symptoms and self-reported cognitive function for secondary aims were assessed using the Symptom-Checklist-90 – Revised (SCL-90-R). Results: In a sample of 86 patients [mean (M) age: 64.6 ± 9.2; Mini-Mental State Examination (MMSE), 3–7 days post-stroke: M = 28.4 ± 1.7; National Institutes of Health Stroke Scale (NIHSS) after 3 months: M = 0.7 ± 1.6] depressive symptoms (HADS) were associated with poorer memory performance after controlling for age, sex, and education (p ≤ .01). In a subsample (n = 41; Age: M = 65.7 ± 8.1; MMSE: M = 28.4 ± 1.8; NIHSS: M = 1.0 ± 1.9), symptoms of phobic anxiety (SCL-90-R) were associated with poorer performance-based memory and attention/executive function, and symptoms of anxiety (SCL-90-R) with lower attention/executive function. Higher levels of self-reported cognitive difficulties were associated with higher scores in all psychiatric domains (p ≤ .05). Conclusion: Even in relatively well-functioning stroke patients, depressive symptoms are associated with poorer memory. The results also suggest that various psychiatric symptoms are more related to self-reported rather than to performance-based cognitive function. Screening for self-reported cognitive difficulties may not only help to identify patients with cognitive impairment, but also those who need psychological treatment.


Author(s):  
Naoki Ishii ◽  
Takujiro Homma ◽  
Jaeyong Lee ◽  
Hikaru Mitsuhashi ◽  
Ken-ichi Yamada ◽  
...  

Abstract Superoxide dismutase 1 suppresses oxidative stress within cells by decreasing the levels of superoxide anions. A dysfunction of the ovary and/or an aberrant production of sex hormones are suspected causes for infertility in superoxide dismutase 1-knockout mice. We report on attempts to rescue the infertility in female knockout mice by providing two antioxidants, ascorbic acid and/or coenzyme Q10, as supplements in the drinking water of the knockout mice after weaning and on an investigation of their reproductive ability. On the first parturition, 80% of the untreated knockout mice produced smaller litter sizes compared with wild-type mice (average 2.8 vs 7.3 pups/mouse), and supplementing with these antioxidants failed to improve these litter sizes. However, in the second parturition of the knockout mice, the parturition rate was increased from 18% to 44–75% as the result of the administration of antioxidants. While plasma levels of progesterone at 7.5 days of pregnancy were essentially the same between the wild-type and knockout mice and were not changed by the supplementation of these antioxidants, sizes of corpus luteum cells, which were smaller in the knockout mouse ovaries after the first parturition, were significantly ameliorated in the knockout mouse with the administration of the antioxidants. Moreover, the impaired vasculogenesis in uterus/placenta was also improved by ascorbic acid supplementation. We thus conclude that ascorbic acid and/or coenzyme Q10 are involved in maintaining ovarian and uterus/placenta homeostasis against insults that are augmented during pregnancy and that their use might have positive effects in terms of improving female fertility.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Guangming Zhu ◽  
Patrik Michel ◽  
Amin Aghaebrahim ◽  
James T Patrie ◽  
Wenjun Xin ◽  
...  

BACKGROUND AND PURPOSE: To determine whether Perfusion-CT (PCT) adds value to Noncontrast head CT (NCT), CT-Angiogram (CTA) and clinical assessment in patients suspected of acute ischemic stroke. METHODS: We retrospectively reviewed the clinical and imaging data collected in 165 patients with acute ischemic stroke. ASPECTS score was calculated from NCT. CTA was reviewed for site of occlusion and collateral flow score. PCT was used to calculate the volumes of infarct core and ischemic penumbra on admission. Recanalization status was assessed on follow-up imaging. Clinical data included age, time from onset to baseline imaging, time from baseline imaging to reperfusion therapy, time from baseline imaging to recanalization imaging, NIHSS at baseline, treatment type and modified Rankin score (mRS) at 90 days. In a first multivariate regression analysis, we used volume of PCT penumbra and infarct core as outcome, and assessed whether they could be predicted from clinical variables, NCT and/or CTA. In a second multivariate regression analysis, we used mRS at 90 days as outcome, and determined which imaging and clinical variables predicted it best. RESULTS: 165 patients were identified. Mean±SD time from onset to baseline imaging was 6.7±8.7 hrs. 76 had a good outcome (90-day mRS 0-2), 89 had a poor outcome. Mean±SD PCT infarct was 44.8±46.5 ml. Mean±SD PCT penumbra was 47.0±33.9 ml. PCT infarct could be predicted by clinical data, NCT, CTA, and combinations of this data (P<0.05); the best predictive model included the clinical data, plus NCT and CTA. PCT Penumbra could NOT be predicted by clinical data, NCT, and CTA. In terms of predicting mRS at 90 days, all of variables but NCT and CTA were significantly associated with 90-day mRS outcome. The single most important predictor was recanalization status (P<0.001). PCT penumbra volume (P=0.001) was also a predictor of clinical outcome, especially when considered in conjunction with recanalization through an interaction term (P<0.001). CONCLUSION: PCT penumbra represents independent information, which cannot be predicted by clinical, NCT, and CTA data. PCT penumbra is an important determinant of clinical outcome, and adds relevant clinical information compared to a stroke CT work-up including NCT and CTA.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Bruce C Campbell ◽  
Søren Christensen ◽  
Christopher R Levi ◽  
Patricia M Desmond ◽  
Geoffrey A Donnan ◽  
...  

Background and purpose: CT-perfusion (CTP) is widely and rapidly accessible for imaging acute ischemic stroke. However, there has been limited validation of CTP parameters against the more intensively studied MRI perfusion-diffusion mismatch paradigm. We tested the correspondence of CTP with contemporaneous perfusion-diffusion MRI. Methods: Acute ischemic stroke patients <6hr after onset had CTP and perfusion-diffusion MRI within 1hr, before reperfusion therapies. Relative cerebral blood flow (relCBF) and time-to-peak of the deconvolved tissue-residue-function (Tmax) were calculated (standard singular value decomposition deconvolution). The diffusion lesion was registered to the CTP slabs and manually outlined to its maximal visual extent. CT-infarct core was defined as relCBF<31% contralateral mean as previously published using this software. The volumetric accuracy of relCBF core compared to the diffusion lesion was tested in isolation, but also when restricted to pixels with relative time-to-peak (TTP) >4sec, to reduce artifactual false positive low CBF (eg in leukoaraiosis). The MR Tmax>6sec perfusion lesion (previously validated to define penumbral tissue at risk of infarction) was automatically segmented and registered to the CTP slabs. Receiver operating characteristic (ROC) analysis determined the optimal CT-Tmax threshold to match MR-Tmax>6sec, confidence intervals generated by bootstrapping. Agreement of these CT parameters with MR perfusion-diffusion mismatch on co-registered slabs was assessed (mismatch ratio >1.2, absolute mismatch>10mL, infarct core<70mL). Results: In analysis of 98 CTP slabs (54 patients, median onset to CT 190min, median CT to MR 30min), volumetric agreement with the diffusion lesion was substantially improved by constraining relCBF<31% within the automated TTP perfusion lesion ROI (median magnitude of volume difference 9.0mL vs unconstrained 13.9mL, p<0.001). ROC analysis demonstrated the best CT-Tmax threshold to match MR-Tmax>6sec was 6.2sec (95% confidence interval 5.6-7.3sec, ie not significantly different to 6sec), sensitivity 91%, specificity 70%, AUC 0.87. Using CT-Tmax>6s “penumbra” and relCBF<31% (restricted to TTP>4s) “core”, volumetric agreement was sufficient for 90% concordance between CT and MRI-based mismatch status (kappa 0.80). Conclusions: Automated CTP mismatch classification using relCBF and Tmax is similar to perfusion-diffusion MRI. CTP may allow more widespread application of the “mismatch” paradigm in clinical practice and trials.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Janet Prvu Bettger ◽  
Xin Zhao ◽  
Cheryl Bushnell ◽  
Louise Zimmer ◽  
Ying Xian ◽  
...  

Background: Socioeconomic status (SES) is widely recognized as an area of inequity that affects health outcomes. However, social determinants of health are less frequently measured in longitudinal studies of acute stroke patients. The relationship of SES on disability 3-months post-stroke is unknown. Methods: We analyzed ischemic stroke patients in the AVAIL registry who were enrolled at 98 hospitals participating in Get With The Guidelines-Stroke. Patients who died (n=64) or did not complete a modified Rankin Scale (mRS) at 3-months (n=154) were excluded. Multivariable logistic regression was used to examine the relationship of SES (defined by level of education, work status, and perceived adequacy of household income to meet needs) and disability (mRS scores 3-5). Results: Among the 2092 stroke patients who met eligibility criteria, the mean age was 65.5 ± 13.7, 44.2% were female, and 82.7% were White. Fifty seven percent had a high school or less education, 11.4% were not working post-stroke and were home not by choice, and 25.7% were without an adequate household income. A third of the sample had some level of disability at 3-months (34.6% mRS 3-5). Those with disability were more likely to be older, non-White, female, single, less educated, have inadequate income, and were home not by choice. In the multivariable analysis, lower education, inadequate income, and being home but not by choice (compared with those who returned to work) were independently associated with disability (p<0.01; Table ). Conclusion: In this national cohort of stroke survivors, socioeconomic status as measured by level of education, work status, and income were independently associated with post-stroke disability.


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