Abstract WP70: Aptamer Inhibition of Von Willebrand Factor Ameliorates Ischemic Stroke Burden in a Murine Model of Thromboembolic Stroke
| Autor: | Jenna Wilson, Debra G Wheeler, Allyson Huttinger, David Dornbos, Spencer Talentino, Jay L. Zweier, Cheyenne Jones, Chandan K. Sen, Cameron Rink, Nicholas Musgrave, Hallie Harris, Nicholas Venetos, Shahid M Nimjee, Camille Bratton, Surya Gnyawali, Kendyl Carlisle |
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| Rok vydání: | 2018 |
| Předmět: |
medicine.medical_specialty
Aptamer 02 engineering and technology Thromboembolic stroke 010402 general chemistry 01 natural sciences Von Willebrand factor Internal medicine medicine Significant risk Recombinant tissue plasminogen activator Stroke Advanced and Specialized Nursing biology business.industry 021001 nanoscience & nanotechnology medicine.disease 0104 chemical sciences Murine model Ischemic stroke Cardiology biology.protein Neurology (clinical) 0210 nano-technology Cardiology and Cardiovascular Medicine business |
| Zdroj: | Stroke. 49 |
| ISSN: | 1524-4628 0039-2499 |
| DOI: | 10.1161/str.49.suppl_1.wp70 |
| Popis: | Introduction: While recombinant tissue plasminogen activator (rTPA) is the mainstay of ischemic stroke treatment, recanalization is only achieved in 25-50% of patients. With a significant risk of intracranial hemorrhage, its use has been limited to within 4.5 hours of symptom onset. Previous work has demonstrated that aptamer inhibition of Von Willebrand Factor (VWF) effectively restores reperfusion following murine carotid artery occlusion. Hypothesis: We tested the hypothesis that VWF aptamer would promote recanalization following thrombotic middle cerebral artery (MCA) occlusion, ameliorating stroke burden with greater efficacy than rTPA. Methods: Adult wild-type (C57BL/6J) mice were anesthetized, and the right carotid artery was exposed. A 32-gauge intracranial catheter was advanced within the carotid artery. Murine autologous blood was then mixed with 10 μL 0.9% normal saline and 1 μL murine thrombin and was allowed to stabilize at 37 °C for 15 minutes, after which it was injected through the catheter into the MCA. Laser-doppler flowmetry monitoring measured decreased flow following injection of the embolus. Treatment (vehicle, platelet binding buffer, n=5; VWF aptamer, n=6; rTPA, n=7) was initiated 20 minutes after thrombus injection. An MRI was obtained at 24 hours to assess ischemic stroke volumes. Results: None of the mice receiving rTPA survived to 24 hours, while all mice treated with VWF aptamer and vehicle survived to 24 hours and received an MRI. Ischemic stroke volume was significantly decreased in mice treated with VWF aptamer (5.49 ± 5.01 mm 3 ) compared to vehicle (35.34 ± 9.57 mm 3 , p Conclusions: Treatment with VWF aptamer decreases stroke volume on MRI in a murine model of embolic stroke without the risk of hemorrhagic conversion seen in patients treated rTPA. VWF inhibition represents a promising therapy in stroke treatment. |
| Databáze: | OpenAIRE |
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