Ischemic stroke results from arterial occlusion causing focal cerebral ischemia with a penumbra of hypoxic but viable tissue (therapeutic window for thrombolysis). Hemorrhagic stroke causes mass effect, increased ICP, and secondary ischemia. Both trigger inflammatory cascades, excitotoxicity, and neuronal death.
Understand the ischemic cascade: loss of ATP → loss of ion homeostasis → calcium influx → protease activation and ROS. Study acute imaging (CT for hemorrhage, MRI DWI for ischemia) and time-based intervention thresholds.
MRI DWI hyperintensity appears within minutes of ischemia, not hours—timing is crucial for intervention eligibility. Hemorrhagic transformation can occur after thrombolysis in large infarcts; this is a known risk, not a contraindication.
From your study of cerebral circulation, you know that the brain is metabolically exceptional: it constitutes 2% of body weight but consumes 20% of cardiac output and has essentially no energy reserves. Cerebral autoregulation normally maintains constant blood flow across a wide range of perfusion pressures. Stroke is what happens when that flow is interrupted — either because a vessel is blocked (ischemic stroke, ~87% of cases) or because one ruptures (hemorrhagic stroke, ~13%). The mechanisms, imaging findings, and treatment windows differ sharply between them.
In ischemic stroke, a thrombus (arising from atherosclerotic plaque) or embolus (typically from cardiac sources like atrial fibrillation, the mechanism you know from thrombosis pathophysiology) occludes a cerebral artery. Downstream tissue is deprived of both oxygen and glucose. The ischemic injury is not homogeneous: the core — directly supplied by the occluded vessel — loses perfusion almost immediately and undergoes rapid irreversible necrosis. Surrounding it is the penumbra: tissue with reduced but not zero perfusion, metabolically stressed but still viable for a window of time. The penumbra is the therapeutic target. ATP depletion causes failure of the Na⁺/K⁺-ATPase, ions flow down their gradients, intracellular sodium and calcium accumulate, and neurons depolarize abnormally. Excitotoxicity follows: excessive glutamate release activates NMDA receptors, allowing massive calcium influx that activates proteases, lipases, and endonucleases — the same cascade you studied in necrosis pathways. The penumbra converts to core at a rate of roughly 1.9 million neurons per minute if perfusion is not restored. This is the biological basis for the maxim "time is brain."
The therapeutic implication is a race against the penumbra's shrinkage. Intravenous thrombolysis (tPA) within 4.5 hours can dissolve the clot and restore flow to viable penumbral tissue. Mechanical thrombectomy (physically retrieving the clot) extends the window to 24 hours in selected patients with imaging-confirmed salvageable penumbra. CT is done first because it rapidly excludes hemorrhage — tPA given to a hemorrhagic stroke would be catastrophic. MRI diffusion-weighted imaging (DWI) shows ischemic core within minutes because restricted water diffusion in cytotoxically swollen cells appears bright before structural necrosis is visible on conventional imaging.
Hemorrhagic stroke operates by an entirely different mechanism. Rupture of a vessel — from hypertensive arteriolar damage, an aneurysm, or an arteriovenous malformation — floods the parenchyma or subarachnoid space with blood. The hematoma exerts mass effect: it compresses surrounding tissue, raises intracranial pressure, and can shift the brain across the midline (herniation). Elevated ICP also secondarily reduces cerebral perfusion pressure, creating ischemia around the bleed — hence "secondary ischemia" in hemorrhagic stroke. The inflammatory response to blood products then compounds injury over the following days. Treatment is the reverse of ischemic stroke: instead of restoring flow, the goal is hematoma control, ICP management, and reversal of any anticoagulation that may have precipitated the bleed. The distinction between hemorrhagic and ischemic stroke cannot be made clinically — imaging is mandatory before any treatment decision, because a drug that saves an ischemic stroke patient can kill a hemorrhagic one.