Cerebral Ischemia Reperfusion in a Large Animal Model

Date of Award

Spring 1-1-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Investigative Medicine

First Advisor

Sestan, Nenad

Abstract

Ischemia reperfusion injury is a fundamental problem in cardio- and cerebrovascular medicine. Thisthesis describes the mechanisms of organ ischemia and recovery, with a primary focus on cerebral ischemia reperfusion injury. We develop a live porcine model of cerebral ischemia reperfusion to bridge the translational gap in cerebral ischemia research. The model is validated by multimodal imaging, histopathology, and transcriptomic sequencing, providing a robust framework for studying neuroprotection and therapeutic interventions. Expanding upon these principles, we also examined the burden of ischemic stroke following cardiovascular interventions, demonstrating procedure-specific variations in stroke incidence and severity. Additionally, we performed a network meta-analysis comparing cerebral protection strategies during circulatory arrest, identifying optimal techniques for cerebral protection during complex cardiac surgery. Lastly, we studied postmortem brain recovery using perfusion technology, extending metabolic viability up to 24 hours postmortem with preserved cellular and blood-brain-barrier integrity. By integrating translational cerebral ischemia reperfusion modeling and organ recovery strategies with clinical outcomes data, this work advances our understanding of cerebral ischemia reperfusion injury and lays the groundwork for novel therapeutic approaches to cerebral ischemia reperfusion injury.

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