UC Davis

The primary goal of stroke research is to improve outcomes and to reduce morbidity and mortality for stroke patients. Although stroke symptoms vary greatly from patient to patient, preclinical research has heavily relied on rodent models for mimicking the stroke condition, aiming to elucidate the mechanisms of stroke and to test potential interventions in a controlled setting. The first chapter discusses our current understanding of the pathophysiology of ischemic stroke, including processes like the formation of the ischemic penumbra, cerebral edema, and neuroinflammation, and explores the benefits and limitations of rodent stroke models. We also compare the temporal development of an infarct, and its associated functional outcomes, in rodent models to what is observed in human patients.

In chapters 2 and 3, we explore immunocytoprotective drug candidates for ischemic stroke. Despite advances in stroke treatment, there are currently only two treatment options available for ischemic stroke that have been shown to improve outcomes, both of which are usually administered within the “early” hours after stroke onset: thrombolysis at <4.5 hours and thrombectomy at <6 hours. In this dissertation, we explore K+ channel blockers as drug candidates that, when used in conjunction with thrombectomy, target neuroinflammation at “later” time points in ischemic stroke, showing that both KV1.3 blockers and KCa3.1 blockers reduce infarct size and improve neurological deficits 8 days post-stroke in rodent stroke models when administered at least 12 hours post-stroke.

In the last chapter, we examine the broader implications of ischemic stroke, its significant economic burden on the United States and its disproportionate effects on minority racial groups. Lastly, we close by discussing the future directions of stroke research, and the roles immunocytoprotective drugs like KV1.3 and KCa3.1 blockers may play as adjunctive therapies for enhancing the benefits of thrombectomy/reperfusion. Future preclinical research must incorporate and adapt to the technological advances, changes, and needs of the present stroke field so that we can maximize outcomes for all stroke patients.