دورية أكاديمية
Effects of Dabigatran in Mouse Models of Aging and Cerebral Amyloid Angiopathy
| العنوان: | Effects of Dabigatran in Mouse Models of Aging and Cerebral Amyloid Angiopathy |
|---|---|
| المؤلفون: | Michael, Neethu, Grigoryan, Mher Mahoney, Kilday, Kelley, Sumbria, Rachita K., Vasilevko, Vitaly, van Ryn, Joanne, Cribbs, David H., Paganini-Hill, Annlia, Fisher, Mark J. |
| المصدر: | Pharmacy Faculty Articles and Research |
| بيانات النشر: | Chapman University Digital Commons |
| سنة النشر: | 2019 |
| المجموعة: | Chapman University Digital Commons |
| مصطلحات موضوعية: | aging, cerebral amyloid angiopathy, cerebral microhemorrhage, dabigatran, direct thrombin inhibitor, intracerebral hemorrhage, Animal Experimentation and Research, Medical Neurobiology, Nervous System Diseases, Other Chemicals and Drugs, Other Pharmacy and Pharmaceutical Sciences, Pharmaceutical Preparations, Therapeutics |
| الوصف: | Oral anticoagulants are a critical component of stroke prevention, but carry a risk of brain hemorrhage. These hemorrhagic complications tend to occur in elderly individuals, especially those with predisposing conditions such as cerebral amyloid angiopathy (CAA). Clinical evidence suggests that non-vitamin K antagonist oral anticoagulants are safer than traditional oral anticoagulants. We analyzed whether the anticoagulant dabigatran produces cerebral microhemorrhage (the pathological substrate of MRI-demonstrable cerebral microbleeds) or intracerebral hemorrhage in aged mice with and without hemorrhage-predisposing angiopathy. We studied aged (22 months old) Tg2576 (a model of CAA) and wild-type (WT) littermate mice. Mice received either dabigatran etexilate (DE) (Tg N = 7; WT N = 10) or vehicle (Tg N = 9; WT N = 7) by gavage for 4 weeks. Anticoagulation effects of DE were confirmed using thrombin time assay. No mice experienced intracerebral hemorrhage. Cerebral microhemorrhage analysis, performed using Prussian-blue and H&E staining, showed no significant change in either number or size of cerebral microhemorrhage in DE-treated animals. Analysis of biochemical parameters for endothelial activation (ICAM-1), blood-brain barrier disruption (IgG, claudin-5, fibrinogen), microglial activation (Iba-1), or astrocyte activation (GFAP) showed neither exacerbation nor protective effects of DE in either Tg2576 or WT mice. Our study provides histological and biochemical evidence that aged mice, with or without predisposing factors for brain hemorrhage, tolerate anticoagulation with dabigatran. The absence of dabigatran-induced intracerebral hemorrhage or increased frequency of acute microhemorrhage may provide some reassurance for its use in high-risk patient populations. |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | https://digitalcommons.chapman.edu/pharmacy_articles/855Test; https://digitalcommons.chapman.edu/cgi/viewcontent.cgi?article=1858&context=pharmacy_articlesTest |
| الإتاحة: | https://digitalcommons.chapman.edu/pharmacy_articles/855Test https://digitalcommons.chapman.edu/cgi/viewcontent.cgi?article=1858&context=pharmacy_articlesTest |
| حقوق: | The authors ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.D01B7081 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |