The ischemic penumbra can be defined in many ways, based on measurements of electrophysiologic function, cerebral blood flow, metabolism, and gene expression. But perhaps the most clinically relevant definition is the pharmacologic penumbra, i.e. any brain tissue that can be salvaged after stroke. In theory, there are two non-mutually exclusive ways to salvage the penumbra: hemodynamic reperfusion and pharmacologic treatment. In this presentation, we will (1) review the experimental animal model data to verify how robust neuroprotection data really are for permanent versus transient focal cerebral ischemia, (2) examine the profiles of penumbral collapse as defined by spreading peri-infarct depolarizations with or without reperfusion, and (3) assess existing in vivo imaging data to see how the penumbra responds to reperfusion and therapy. If available, data from the SAINT trials that combine tPA with NXY-059 may also be discussed. Overall, these experimental and clinical data may give insight into the question of whether true neuroprotection in stroke is feasible in the absence of reperfusion.
