Objectives: No single animal stroke model satisfies all needs of translational stroke investigation. While the nylon filament MCAo model is widely accepted in preclinical translational stroke research, thromboembolic models have more physiological relevance. Thromboembolic models are technically difficult, time consuming, and show variable results, however, rendering them less utilizable for widespread deployment in a multi-laboratory preclinical network. We sought to develop and validate a standardized thromboembolic middle cerebral artery occlusion model that encompasses vessel occlusion and subsequent thrombolysis. Methods: To reduce the numbers of donor animals required, we developed a method to store donor blood for later use. Using prefabricated microcatheters, we simplified thrombus preparation and handling. For thrombolysis we used intravenous Tenecteplase dosing at 1.5mg/kg. To demonstrate feasibility and ease-of-use, the model was implemented at six research laboratories. We wrote and field-tested standard operating procedures, training videos, and hands-on surgical training workshops. Results: We enrolled 170 Sprague Dawley rats—some of which were only used as blood donors—of both sexes at six laboratories which performed 4 to 6 thrombus embolizations per week. All laboratories achieved reproducible occlusion and thrombolysis. Thromboemboli prepared from stored blood worked as well as emboli from freshly drawn blood. Of 135 rats who received one embolus, 33 (24%) died before 48-hour MRI scan. In survivors, stroke volume was 13±16% of the ipsilateral hemisphere. Corner test, neurobehavioral battery, and MRI showed reasonably consistent stroke injury. Conclusions: We established the feasibility and reproducibility of a multi-laboratory rodent thromboembolic model. All sites, including novice surgeons, mastered the surgical protocol. Numbers of surgeries per week would allow high-throughput testing.
Lin et al. (Thu,) studied this question.