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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AbstractBackgroundPatients with NAFLD are considered at a high risk of cardiovascular events due to underlying metabolic risk factors. Currently, data related to the impact of NAFLD on cardiovascular risk in the general population are lacking.AimsThe aim of this study was to investigate the role of NAFLD on risk of myocardial infarction (MI), coronary heart disease (CHD), atrial fibrillation (AF), and stroke in primary care in Germany.MethodsThe study included patients diagnosed with NAFLD in primary care between 2010 and 2015. NAFLD cases (n = 22,048) were matched to a cohort without NAFLD (n =&thinsp...
Source: Digestive Diseases and Sciences - Category: Gastroenterology Source Type: research
Authors: Isordia-Salas I, Martínez-Marino M, Alberti-Minutti P, Ricardo-Moreno MT, Castro-Calvo R, Santiago-Germán D, Alvarado-Moreno JA, Calleja-Carreño C, Hernández-Juárez J, Leaños-Miranda A, Majluf-Cruz A Abstract Background and Purpose: The thrombin-activatable fibrinolysis inhibitor (TAFI) is an important inhibitor of fibrinolysis and plays a critical role in the pathogenesis of arterial thrombosis; genetic polymorphisms of the TAFI gene affect its activity and increase the risk of thrombosis. Moreover, studies in young patients are still scarce. The aim was to examin...
Source: Disease Markers - Category: Laboratory Medicine Tags: Dis Markers Source Type: research
CONCLUSION: The optimal management of modifiable risk factors may be important for preventing dementia in subjects with diabetes mellitus. PMID: 31769236 [PubMed - as supplied by publisher]
Source: Diabetes and Metabolism Journal - Category: Endocrinology Tags: Diabetes Metab J Source Type: research
This study aimed to assess the associations of pregnancy loss and risk of hypertension, type 2 diabetes (T2D), and hypercholesterolemia.
Source: Obstetric Anesthesia Digest - Category: Anesthesiology Tags: Mother, Fetus, Neonate Source Type: research
ConclusionAspirin reduced the risks of MACCE and cancer without increasing the bleeding risk in elderly Koreans with hypertension, T2DM, or dyslipidemia. Moreover, the benefits of the long-term use of aspirin in reducing the risks of MACCE were demonstrated. However, the decision of using aspirin for primary prevention must be carefully made on an individual basis, while estimating the benefit –risk balance of aspirin.
Source: Drugs and Aging - Category: Geriatrics Source Type: research
Conclusions: Our study provides a nationwide, population based, 13-year retrospective data demonstrating that OSA patients are at a higher risk of female infertility.Keywords: Obstructive sleep apnea; Female infertility; Taiwan National Health Insurance Research Database; Longitudinal Health Insurance Database
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Sleep and control of breathing Source Type: research
Conclusion: This study suggests that smoking may have a greater impact on the development of stroke (p = 0.012) and HBP (p = 0.025). Smoking also has an impact on the development of AMI, but on a smaller scale (p=0.042). Higher PY values are also influencing the development of CVD (p = 0.035). There was no statistically significant variation between the two groups in the development of DM2.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Tobacco, smoking control and health educ. Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
ConclusionsDiabetic nephropathy was common among Chinese patients with type 2 diabetes in primary care in Hong Kong. Early identification and control of the modifiable risk factors are of upmost importance in preventing the complication.
Source: Journal of Diabetes and Metabolic Disorders - Category: Endocrinology Source Type: research
Publication date: Available online 6 November 2019Source: JACC: Heart FailureAuthor(s): Milton PackerAbstractBoth obesity and type 2 diabetes are important risk factors for the development of heart failure with a preserved ejection fraction (HFpEF), and both disorders increase the risk of systemic thromboembolic events. Traditionally, the risk of stroke has been explained by the strong association of these disorders with atrial fibrillation (AF). However, adiposity and diabetes are risk factors for systemic thromboembolism, even in the absence of AF, because both can lead to the development of an inflammatory and fibrotic ...
Source: JACC: Heart Failure - Category: Cardiology Source Type: research
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