Current approach in thrombolytic therapy research – how to break the translational block.
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| Year of publication | 2024 |
| Type | Conference abstract |
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| Description | In vivo preclinical research on thrombolytic therapy of stroke is complicated in terms that the thrombolysis efficacy and the thrombolysis treatment safety cannot be evaluated simultaneously. Therefore, we developed two models for testing new thrombolytics and new dual treatment methods. The thrombolysis “efficacy model” is performed with continuous X-ray scanning of artificial clots embolized into the systemic circulation in rats. Artificial clots are human fibrin based and barium labelled. The model has zero mortality (0 from 174) and in animal including to study is 100% success rate (174 from 174) in minimally one clot lysis tracking/rat. The safety study model is based on “classic” thromboembolic Middle Cerebral Artery Occlusion and uses the same type of clot as the “efficacy model”. However, accepted is all embolization to the large cerebral vessels (anterior, middle, or posterior cerebral artery). Thrombolysis is initiated four hours after stroke induction. After 24 hours, the brain is impregnated for micro computed tomography (miCT) examination and haemorrhagic transformation is detected and quantified. Brain sections can be further processed using topographic mass spectrometry (LA-ICP-MS) and histology. The presented novel approach for thrombolytics treatment testing in stroke with two complementary models allows for streamlining preclinical research by reducing the number of animals used, almost 100% inclusion of experimental subjects for data processing. |
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