Introduction: Stroke is the 4th leading cause of death in the U.S. with 130,000 deaths and around 795,000 affected annually. At present there is a significant disconnect between basic stroke research and clinical stroke therapeutic needs. To bridge this divide, we have retro-engineered a mouse model of stroke from clinical ischemic stroke thrombectomy for selective intra-arterial pharmacotherapy administration.
Methods: Stroke was induced using the tandem transient common carotid and middle cerebral artery occlusion (MCAO) model. Ischemia was verified using a laser doppler to measure a decrease in blood flow through the occluded middle cerebral artery and laser speckle to measure a decrease in ipsilateral hemispheric blood flow. Both laser doppler and speckle were used to confirm reperfusion of the affected vessel. We then threaded micro-angio tubing into the external carotid artery towards the bifurcation of the common carotid and internal carotid arteries allowing for the delivery of agents to the site of acute ischemia. Next, our model was optimized through a flow rate and injection volume study using carbon black ink injected through the intra-arterial model at different flow rates and injection volumes.
Results: The purpose of this study was to demonstrate our injections were arriving at the site of ischemia and to improve injection volumes for future dosing while mitigating systemic side effects. We determined that a flow rate of 2.5µl/minute and injection volume of 10µl was optimal. This was done through an examination of dorsal aspect and Circle of Willis of the brain as well as a cross sectional view of the liver.
Conclusions: This suggests that our stroke model may improve the preclinical validation of potential stroke therapies and help bridge the bench to bedside divide in developing new stroke therapies.
Patient Care: This research will provide relevant opportunities to study stroke paradigm clinically related to patient care.
Learning Objectives: 1) Describe issues related to translation from bench to bedside and back to bench.
2) Understand clinically relevant animals models of stroke.
3) Validation of animal models of stroke.