Delayed Administration of Angiotensin II Type 2 Receptor (AT2R) Agonist Compound 21 Prevents the Development of Post-stroke Cognitive Impairment in Diabetes Through the Modulation of Microglia Polarization

AbstractA disabling consequence of stroke is cognitive impairment, occurring in 12% –48% of patients, for which there is no therapy. A critical barrier is the lack of understanding of how post-stroke cognitive impairment (PSCI) develops. While 70% of stroke victims present with comorbid diseases such as diabetes and hypertension, the limited use of comorbid disease models in prec linical research further contributes to this lack of progress. To this end, we used a translational model of diabetes to study the development of PSCI. In addition, we evaluated the application of compound 21 (C21), an angiotensin II Type 2 receptor agonist, for the treatment of PSCI by blinding the treatment assignment, setting strict inclusion criteria, and implementing a delayed administration time point. Diabetes was induced by a high-fat diet (HFD) and low-dose streptozotocin (STZ) combination. Control and diabetic rats were subjected to 1 h middle cerebral artery occlusion (MCAO) or sham surgery. Adhesive removal task (ART) and two-trial Y-maze were utilized to test sensorimotor and cognitive function. Three days post-stroke, rats that met the inclusion criteria were administered C21 or vehicle in drinking water at a dose of 0.12 mg/kg/day for 8 weeks. Samples from freshly harveste d brains were analyzed by flow cytometry and immunohistochemistry (IHC). Diabetes exacerbated the development of PSCI and increased inflammation and demyelination. Delayed administration of C21 3 days post-stro...
Source: Translational Stroke Research - Category: Neurology Source Type: research

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ConclusionTransgender and gender diverse individuals represent a population who express various gender identities and are seeking gender-specific healthcare at increasing rates. Psychiatric illness is highly prevalent compared to the US population but there is no difference in the prevalence of CV risk factors including obesity, type 2 diabetes, hypertension, and dyslipidemia.
Source: Biology of Sex Differences - Category: Biology Source Type: research
In this study, the clinical significance of serum RAGE levels in acute ischemic stroke patients with type 2 diabetes was determined.MethodThree hundred seven patients (165 patients without diabetes and 142 patients with diabetes) with acute cerebral infarction (ACI) were enrolled over 3 consecutive months. On admission, their National Institute of Health Stroke Scale (NIHSS) scores were recorded. The clinical laboratory data of all subjects were collected, and their serum levels of RAGE were assayed using enzyme-linked immunosorbent assay (ELISA). On admission and 3 months after stroke, the clinical outcomes were assessed ...
Source: Irish Journal of Medical Science - Category: General Medicine Source Type: research
In conclusion, it remains unclear if brain-specific regional and temporal changes occur in the expression of the different APP variants during AD progression. Since APP is also found in blood cells, assessing the changes in APP mRNA expression in peripheral blood cells from AD patients has been considering an alternative. However, again the quantification of APP mRNA in peripheral blood cells has generated controversial results. Brain APP protein has been analyzed in only a few studies, probably as it is difficult to interpret the complex pattern of APP variants and fragments. We previously characterized the soluabl...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Obesity is responsible for multiple chronic diseases, including type 2 diabetes, hypertension, coronary artery disease, stroke, and several types of cancer [1]. The body mass index (BMI) —as an easy-to obtain, acceptable proxy for thinness and fatness—has been found to be associated with health risk and death in many populations. According to the World Health Organization definition, the normal range of BMI is defined as 18.5 to
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
This study is the first to provide a direct link between this inflammation and plaque development - by way of IFITM3. Scientists know that the production of IFITM3 starts in response to activation of the immune system by invading viruses and bacteria. These observations, combined with the new findings that IFITM3 directly contributes to plaque formation, suggest that viral and bacterial infections could increase the risk of Alzheimer's disease development. Indeed, researchers found that the level of IFITM3 in human brain samples correlated with levels of certain viral infections as well as with gamma-secretase activ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Dapagliflozin Influences Ventricular Hemodynamics and Exercise-Induced Pulmonary Hypertension in Type 2 Diabetes Patients - A Randomized Controlled Trial. Circ J. 2020 Sep 12;: Authors: Kayano H, Koba S, Hirano T, Matsui T, Fukuoka H, Tsuijita H, Tsukamoto S, Hayashi T, Toshida T, Watanabe N, Hamazaki Y, Geshi E, Murakami M, Aihara K, Kaneko K, Yamada H, Kobayashi Y, Shinke T Abstract BACKGROUND: This prospective randomized multicenter open-label trial evaluated whether sodium-glucose cotransporter-2 inhibitor (SGLT2-i) improves left ventricular (LV) pump function and suppresses elevation of LV fill...
Source: Circulation Journal - Category: Cardiology Authors: Tags: Circ J Source Type: research
In conclusion, using a large cohort with rich health and DNA methylation data, we provide the first comparison of six major epigenetic measures of biological ageing with respect to their associations with leading causes of mortality and disease burden. DNAm GrimAge outperformed the other measures in its associations with disease data and associated clinical traits. This may suggest that predicting mortality, rather than age or homeostatic characteristics, may be more informative for common disease prediction. Thus, proteomic-based methods (as utilised by DNAm GrimAge) using large, physiologically diverse protein sets for p...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: Chrysant SG, Chrysant GS Abstract INTRODUCTION: Hypertension and cardiovascular diseases (CVD) are very common conditions and account for significant medical disability and death worldwide. Therefore, their successful management is very critical for the prevention of the significant cardiovascular and socioeconomic consequences arising from their poor management. Areas Covered: Although we have several effective cardiovascular (CV) drugs for their treatment, they are not all completely successful for the effective management of CVD and hypertension. Thus, the need for the discovery and development of new d...
Source: Expert Opinion on Drug Safety - Category: Drugs & Pharmacology Tags: Expert Opin Drug Saf Source Type: research
In this study, we sought to elucidate the role of VRK-1 in regulation of adult life span in C. elegans. We found that overexpression of VRK-1::GFP (green fluorescent protein), which was detected in the nuclei of cells in multiple somatic tissues, including the intestine, increased life span. Conversely, genetic inhibition of vrk-1 decreased life span. We further showed that vrk-1 was essential for the increased life span of mitochondrial respiratory mutants. We demonstrated that VRK-1 was responsible for increasing the level of active and phosphorylated form of AMPK, thus promoting longevity. A Fisetin Variant, C...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Conclusion: Dapagliflozin seemingly influences systemic and renal hemodynamics independently and beyond glucose lowering in people with type 2 diabetes. This clinical trial was registered at https://clinicalTrials.gov (ID: NCT02682563).
Source: Journal of Hypertension - Category: Cardiology Tags: ORIGINAL PAPERS: Treatment Source Type: research
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