دورية أكاديمية
Effects of Phosphodiesterase 3A Modulation on Murine Cerebral Microhemorrhages
| العنوان: | Effects of Phosphodiesterase 3A Modulation on Murine Cerebral Microhemorrhages |
|---|---|
| المؤلفون: | Sumbria, Rachita K., Vasilevko, Vitaly, Grigoryan, Mher Mahoney, Paganini-Hill, Annlia, Kim, Ronald, Cribbs, David H., Fisher, Mark J. |
| المصدر: | Pharmacy Faculty Articles and Research |
| بيانات النشر: | Chapman University Digital Commons |
| سنة النشر: | 2017 |
| المجموعة: | Chapman University Digital Commons |
| مصطلحات موضوعية: | Phosphodiesterase 3A, Cerebral microhemorrhage, Cerebral microbleeds, Cilostazol, Cerebral amyloid angiopathy, Animal Experimentation and Research, Medical Neurobiology, Nervous System Diseases, Other Chemicals and Drugs, Other Pharmacy and Pharmaceutical Sciences, Pharmaceutical Preparations, Therapeutics |
| الوصف: | Background: Cerebral microbleeds (CMB) are MRI-demonstrable cerebral microhemorrhages (CMH) which commonly coexist with ischemic stroke. This creates a challenging therapeutic milieu, and a strategy that simultaneously protects the vessel wall and provides anti-thrombotic activity is an attractive potential approach. Phosphodiesterase 3A (PDE3A) inhibition is known to provide cerebral vessel wall protection combined with anti-thrombotic effects. As an initial step in the development of a therapy that simultaneously treats CMB and ischemic stroke, we hypothesized that inhibition of the PDE3A pathway is protective against CMH development. Methods: The effect of PDE3A pathway inhibition was studied in the inflammation-induced and cerebral amyloid angiopathy (CAA)-associated mouse models of CMH. The PDE3A pathway was modulated using two approaches: genetic deletion of PDE3A and pharmacological inhibition of PDE3A by cilostazol. The effects of PDE3A pathway modulation on H&E- and Prussian blue (PB)-positive CMH development, BBB function (IgG, claudin-5, and fibrinogen), and neuroinflammation (ICAM-1, Iba-1, and GFAP) were investigated. Results: Robust development of CMH in the inflammation-induced and CAA-associated spontaneous mouse models was observed. Inflammation-induced CMH were associated with markers of BBB dysfunction and inflammation, and CAA-associated spontaneous CMH were associated primarily with markers of neuroinflammation. Genetic deletion of the PDE3A gene did not alter BBB function, microglial activation, or CMH development, but significantly reduced endothelial and astrocyte activation in the inflammation-induced CMH mouse model. In the CAA-associated CMH mouse model, PDE3A modulation via pharmacological inhibition by cilostazol did not alter BBB function, neuroinflammation, or CMH development. Conclusions: Modulation of the PDE3A pathway, either by genetic deletion or pharmacological inhibition, does not alter CMH development in an inflammation-induced or in a CAA-associated mouse model of CMH. ... |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | https://digitalcommons.chapman.edu/pharmacy_articles/858Test; https://digitalcommons.chapman.edu/cgi/viewcontent.cgi?article=1861&context=pharmacy_articlesTest |
| الإتاحة: | https://digitalcommons.chapman.edu/pharmacy_articles/858Test https://digitalcommons.chapman.edu/cgi/viewcontent.cgi?article=1861&context=pharmacy_articlesTest |
| حقوق: | The authors ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.82EA9BE6 |
| قاعدة البيانات: | BASE |
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