Translational aspects of reperfusion in acute ischemic stroke

Despite significant advancements in the treatment of acute ischemic stroke, approximately 50% of patients have poor clinical outcomes, even following successful recanalization of the occluded cerebral artery. This thesis posits that such unfavorable outcomes are, at least in part, attributable to incomplete microvascular reperfusion. Currently, the only acute therapeutic interventions available are recanalization strategies, including intravenous administration of thrombolytics and mechanical endovascular treatment. Furthermore, numerous pharmacological agents that demonstrated efficacy in rodent models have failed to yield positive results in human clinical trials.
To enhance translational success and reduce the initiation of unnecessary clinical trials, the use of large animal models prior to human testing is proposed. This work systematically compares the available large animal models for ischemic stroke, evaluates the vascular damage associated with endovascular procedures, and implements both rat and swine models of recanalized acute ischemic stroke to investigate post-recanalization (microvascular) reperfusion. A deeper understanding of these underlying pathophysiological mechanisms may reveal novel therapeutic targets, ultimately aiming to improve outcomes for patients with ischemic stroke.