Stroke is the one of the leading causes for death and the leading cause of long-term disability in the USA, and most strokes originate from blood flow blockage known as ischemic stroke. Since the majority of cortical ischemic strokes originate from blockage in the middle cerebral artery (MCA), our lab has studied stroke protection in a rat model of permanent middle cerebral artery occlusion (pMCAo). Our findings have demonstrated that sensory stimulation in the early 2 hours following pMCAo is protective but later (3-4 hours) the same stimulation becomes damaging (known as infarct). It is assumed that the location and volume of either the damaged or protected territory depends on the spatial structure of the occluded artery (e.g., MCA), but research results in our lab point to an alternative hypothesis that the location and volume of an infarcted or protected territory depends on the spread of evoked neuronal activity in cortex. To address our hypothesis, we plan to apply state-of-the-art multi-modal battery of in vivo wide-field imaging techniques including blood flow imaging and functional imaging of cortical activity. These imaging techniques are complemented by optogentic stimulation, electrophysiological recordings using microelectrode arrays, histological, pharmacological treatment studies, and by the development of machine learning algorithms. These techniques will be employed to provide an unprecedented spatiotemporal, quantitative understanding on how the spread of evoked activity is pivotal for predicating the location and volume of the infarcted or protected cortical territory. Finally, to increase the translational potential of these studies, these techniques will be applied in old rats that represent the population most vulnerable to stroke, and in awake, head-fixed young and old rats to increase the translational potential of our research.