Ischemic Stroke Pathophysiology (~87% of cases) An ischemic...

Ischemic Stroke Pathophysiology (~87% of cases) An ischemic stroke occurs when a thrombus, embolus, or small vessel occlusion limits cerebral blood flow (CBF). The Ischemic Cascade: ATP Depletion: Cerebral hypoperfusion starves neurons of oxygen and glucose. Without ATP, energy-dependent membrane pumps (\text{Na}^+/\text{K}^+-ATPase) fail. Anoxic Depolarization & Excitotoxicity: Failure of ionic pumps causes massive membrane depolarization, releasing excessive glutamate into the synaptic cleft. Glutamate overstimulates NMDA and AMPA receptors. Intracellular Calcium Influx: Overactivation of NMDA receptors triggers a toxic influx of \text{Ca}^{2+} into the cell. High calcium levels activate destructive enzymes (proteases, lipases, endonucleases) that degrade cellular structures. Free Radical Generation & Apoptosis: Mitochondrial dysfunction produces reactive oxygen species (ROS), leading to oxidative damage, neuroinflammation, and programed cell death. Tissue Zones: Ischemic Core: Irreversibly damaged brain tissue near the blockage site where blood flow drops below ~10 mL/100g/min. Ischemic Penumbra: Hypoperfused tissue surrounding the core that remains functionally silent but metabolically viable if reperfusion occurs promptly.