The Stroke Preclinical Assessment Network Multi-laboratory Model of Thromboembolic Stroke with Thrombolysis: TE-MCAo

Current translational rodent stroke models induce middle cerebral artery occlusion (MCAo) using nylon filaments, injected emboli, intraluminal thrombin, or perivascular endothelin-1 to simulate human stroke. Among these methods, thromboemboli injection followed by thrombolysis best mimics the neuroinflammatory events seen in human patients and may be preferable to the inert nylon filament method most widely used. The standard thromboembolic models, used in leading single laboratories, however, can be time-consuming, produce variable results, and require considerable skill to master. To address these limitations, we developed a thromboembolic MCAo model that targets vessel occlusion and uses intravenous thrombolysis to achieve recanalization, paralleling the systemic thrombolysis administered in clinical scenarios. To reduce the number of animals, we developed a method to store blood from donor animals for later emboli preparation for multiple subjects. Our utilization of prefabricated Doccol microcatheters simplifies thrombus preparation and injection by pre-loading thromboemboli into the microcatheters that are then inserted into the internal carotid artery. To achieve recanalization, we infused intravenous Tenecteplase at a dose of 1.5 mg/kg. To promote reproducibility, we prepared and field-tested standard operating procedures, training videos, and hands-on surgical training workshops. The model uses a standard surgical approach that should be familiar to all investigators who use the widely accepted nylon filament model. Passage of the microcatheter into the distal internal carotid artery, avoiding the pterygopalatine artery, is accomplished in a manner similar to the nylon filament insertion. Recovery and post-stroke assessments may be done with typical behavioral, radiographic, and histologic protocols. This model offers a practical, reproducible, and accessible approach for investigators seeking a thromboembolic MCAo model with controlled recanalization.