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 |
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| المؤلفون: | Neethu Michael, Mher Mahoney Grigoryan, Kelley Kilday, Rachita K. Sumbria, Vitaly Vasilevko, Joanne van Ryn, David H. Cribbs, Annlia Paganini-Hill, Mark J. Fisher |
| المصدر: | Frontiers in neurology, vol 10, iss SEP Frontiers in Neurology, Vol 10 (2019) Frontiers in Neurology |
| بيانات النشر: | Frontiers Media SA, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | cerebral microhemorrhage, Pathology, claudin 5, blood brain barrier, Neurodegenerative, 030204 cardiovascular system & hematology, Fibrinogen, lcsh:RC346-429, immunoglobulin G, 0302 clinical medicine, Psychology, dabigatran, anticoagulation, direct thrombin inhibitor, Original Research, Anticoagulant, Hematology, staining, intercellular adhesion molecule 1, cell activation, 3. Good health, Stroke, aged, female, Neurology, eosin, glial fibrillary acidic protein, ferric ferrocyanide, Cerebral amyloid angiopathy, chemical parameters, medicine.drug, medicine.medical_specialty, medicine.drug_class, animal experiment, Clinical Sciences, bibr 1048 ms, Article, animal tissue, Dabigatran, Angiopathy, Endothelial activation, 03 medical and health sciences, thrombin time, male, Acquired Cognitive Impairment, medicine, biochemistry, controlled study, cerebral amyloid angiopathy, mouse, lcsh:Neurology. Diseases of the nervous system, Intracerebral hemorrhage, nonhuman, business.industry, Prevention, hematoxylin, animal model, aging, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), dabigatran etexilate, vascular amyloidosis, medicine.disease, intracerebral hemorrhage, Brain Disorders, Direct thrombin inhibitor, drug blood level, Dementia, fibrinogen, Neurology (clinical), business, 030217 neurology & neurosurgery |
| 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1664-2295 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a602060daacc9537e4fee5e062b9cb89Test https://doi.org/10.3389/fneur.2019.00966Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a602060daacc9537e4fee5e062b9cb89 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16642295 |
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