Stroke: Penumbra and Reperfusion

Acute ischemic stroke results from arterial occlusion (most commonly middle cerebral artery territory) causing cerebral ischemia. The ischemic core receives <10-12 mL/100g/min blood flow and undergoes irreversible necrosis within minutes (excitotoxic cell death from glutamate release, calcium influx, and mitochondrial failure). Surrounding the core is the ischemic penumbra — functionally impaired but structurally intact tissue receiving 12-22 mL/100g/min. The penumbra represents salvageable brain tissue that is the TARGET of acute stroke treatment. Without reperfusion, the penumbra progressively recruits into the infarct core over hours ('time is brain' — 1.9 million neurons die per minute of untreated large vessel occlusion). Reperfusion strategies: (1) IV alteplase (tPA): within 4.5 hours of symptom onset; dose 0.9 mg/kg (max 90 mg), 10% as bolus, 90% infused over 60 minutes. (2) Mechanical thrombectomy: endovascular clot retrieval for large vessel occlusion (LVO) in anterior circulation, up to 24 hours from symptom onset IF perfusion imaging shows salvageable penumbra (DAWN and DEFUSE-3 trials extended the window). CT perfusion or MRI diffusion-perfusion mismatch identifies the penumbra: the mismatch between the infarcted core (irreversible) and the hypoperfused tissue (salvageable)...