Ischemic stroke results from cerebral artery occlusion (thrombotic or embolic) causing neuronal death from ATP depletion. The ischemic penumbra (tissue at risk surrounding the core infarct) is salvageable with reperfusion. IV alteplase within 4.5 hours (NINDS, ECASS III) or mechanical thrombectomy within 24 hours for large vessel occlusion (DAWN, DEFUSE 3). NIHSS quantifies severity. Door-to-needle time target <60 minutes.