Vascular targets for ischemic stroke treatment

Abstract

The vast majority of studies on stroke therapy have focused on protecting the neuron from hypoxic/ischemic injury. While undoubtedly important, stroke is a vascular disorder affecting not only neurons, but numerous other cell types in the brain including astrocytes, microglia, and vascular cells (endothelium and smooth muscle). In fact, the only effective treatment for ischemic stroke is a vascular one- dissolution of the clot with tissue plasminogen activator and rapid recanalization of an occluded vessel. The failure of every neuroprotective agent to make it into clinical trials highlights the complexity of ischemic stroke pathophysiology that involves inflammation, oxidative stress, and both macro- and micro-vascular dysregulation that causes brain injury itself and exacerbates the primary insult (i.e., secondary brain injury). The vasculature in the brain has a central role in defining stroke injury since the core infarction is dependent on the depth and duration of ischemia. In addition, any neuroprotective therapy for stroke depends on a patent and functional vasculature, further highlighting the importance of vascular protection as an important therapeutic approach to limiting stroke damage.