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Intra-arterial therapy Development in Stroke Pig Models
Abstract
Abstract Body
We are witnessing an enormous impact of endovascular clot removal on outcomes of eligible patients with stroke. This procedure restores blood flow and provides an opportunity for drug delivery to the infarcted area to improve outcomes further. It is particularly compelling to merge mechanical thrombectomy (MT) with intra-arterial drug infusion as a one-stop-shop procedure. Additionally, there is a rapid growth of thrombectomy-capable centers, which may allow to readily use of an intra-arterial route to deliver drugs at a large scale also to MT-ineligible patients, which suffer from a scarcity of therapeutic options. Therefore, there is an urgent need for a highly clinically relevant model capable of restoring blood flow to the infarcted brain to study the therapeutic effect of a variety of potential therapeutic agents. Lisencephalic rodent brains with a low white to gray matter ratio are relatively poor predictors of clinical translations. On the other side, primate and canine stroke models are poorly accessible, prohibitively expensive, and ethically questionable. The pig is the most extensively used large animal in biomedical research. Still, it was not possible to create a porcine model of stroke permitting restoration of blood blow – an condicio sine qua non to recapitulate the current clinical setting due to the rete between extracerebral and intracerebral circulation. We have demonstrated that intra-arterial infusion of thrombin produces a stroke through clot formation, which can be readily dissolved to restore blood flow. Then, we have shown the utility of this model in testing the therapeutic effects of glycolic acid.