Despite
rapid and recent progress in our understanding of numerous new
mechanisms regulating neuronal cell physiology and responses to
ischemia, no neuroprotective agents have been developed as an adjunctive
treatment for acute ischemic stroke. However, with the widespread
deployment of acute tissue perfusion-based stroke imaging and
endovascular thrombectomy, there is a great therapeutic opportunity to
identify patients with salvageable ischemic tissue and provide
neuroprotective treatment along with recanalization that significantly
improves stroke outcome. In this chapter, we review seminal and recent
developments in our understanding of the mechanisms underlying ischemic
large vessel stroke injury including bioenergetic failure,
excitotoxicity, oxidative stress, regulated cell death, and
inflammation. Exciting developments in collaborative translational
research efforts will provide investigators with a blueprint for
systematically testing the most promising therapies preclinically
analogous to clinical trials. Together, these basic, translational, and
clinical advances hold the promise of developing novel neuroprotective
therapies and greatly improving stroke patient outcomes.
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