Ischemic stroke happens when a blood clot or other blockage cuts off blood flow to part of the brain. It accounts for about 65% of all strokes worldwide. The blockage starves brain cells of oxygen and nutrients, and cells begin to die when blood flow drops below roughly 30% of its normal rate. Understanding what triggers that blockage is the key to prevention.
How a Blocked Artery Damages the Brain
Under normal conditions, about 50 mL of blood flows through every 100 grams of brain tissue each minute. When an artery is blocked, that number plummets. The damage unfolds in stages. First, the brain’s ability to build new proteins shuts down. As flow drops further, brain cells switch to a less efficient emergency fuel system that produces lactic acid, making the tissue increasingly acidic. When flow falls to about a third of normal, electrical activity in neurons fails. Below 30% of normal flow, brain cells start dying irreversibly.
The tissue at the center of the blockage, called the infarct core, is the first to die. Surrounding it is a zone called the penumbra, where cells are damaged but still alive because they receive trickle-down blood from neighboring vessels. This penumbra is the reason emergency treatment matters so much. If blood flow is restored quickly, some of that tissue can be saved. If not, the penumbra gradually dies too, expanding the area of permanent damage.
The Two Main Types of Clot
Not all stroke-causing clots are the same. They generally fall into two categories based on where the clot forms.
Thrombotic strokes happen when a clot forms directly inside an artery that supplies the brain. This usually occurs at a spot where fatty plaque has built up on the artery wall, narrowing the channel. The clot grows on top of the plaque and eventually blocks the artery. These clots tend to be loosely organized, with fine nets of fibrin, large numbers of red blood cells, and a fragile structure.
Embolic strokes happen when a clot forms somewhere else in the body, breaks free, and travels through the bloodstream until it lodges in a brain artery too narrow for it to pass. The most common sources are the heart and the large carotid arteries in the neck. These clots are typically denser, more compact, and more stable than thrombotic clots, with thick fibrin networks and high platelet content. In studies of stroke patients who underwent clot-removal procedures, about 44% of strokes were cardioembolic (originating from the heart) and roughly 22% were caused by clots that broke off from diseased arteries.
Atherosclerosis in the Carotid Arteries
Plaque buildup in the carotid arteries, the two large vessels running along each side of your neck, causes about 10 to 20% of all ischemic strokes. This works through two distinct mechanisms, and they can reinforce each other.
The more common mechanism is embolism. A plaque in the carotid wall becomes unstable, or “vulnerable,” and pieces of it break off and travel to the brain. Plaques most likely to cause this have a large core of fatty, dead tissue, a thin or cracked outer cap, signs of internal bleeding, and clusters of inflammatory cells. These features make the plaque fragile and prone to rupture regardless of how much it narrows the artery.
The second mechanism is hemodynamic, meaning the plaque has grown large enough to significantly restrict blood flow. The brain downstream doesn’t get enough pressure to function normally. In practice, these two mechanisms often overlap. Reduced flow makes it harder for the brain to clear small bits of debris, so even tiny fragments that would normally wash away harmlessly can lodge in the brain and cause damage.
Atrial Fibrillation and Other Heart Conditions
The heart is one of the most dangerous sources of embolic clots. Atrial fibrillation, a common irregular heart rhythm, increases the risk of ischemic stroke fivefold. When the upper chambers of the heart quiver instead of contracting properly, blood pools and stagnates, especially in a small pouch called the left atrial appendage. Stagnant blood clots more easily. The shape and structure of that pouch varies from person to person, and some shapes promote more stagnation than others.
Other heart conditions that can send clots to the brain include recent heart attacks (which can damage the inner wall of the heart and create a surface where clots form), mechanical heart valves, and infections of the heart valves. In about a quarter of stroke patients, no clear source for the clot is identified. These are classified as strokes of unknown origin, or cryptogenic strokes.
Small Vessel Disease and Lacunar Strokes
Not all ischemic strokes involve large arteries. Some occur deep inside the brain when tiny penetrating arteries, some barely visible to the naked eye, become diseased and close off. These produce small, deep infarcts called lacunar strokes.
The vascular pathology behind lacunar strokes was mapped in detail by the neurologist C. Miller Fisher, who examined these tiny arteries under a microscope. He found that in many cases the vessel walls had been invaded by fatty, pink-staining material, a process he called lipohyalinosis. The normal layers of the artery wall were sometimes replaced entirely by tangles of connective tissue. Foam cells could fill and block the lumen. In other cases, plaques from a larger parent artery grew over the opening of a small branch vessel, sealing it shut.
When Fisher reviewed the charts of 114 patients who had lacunar strokes confirmed at autopsy, virtually all of them had a history of high blood pressure. The onset of stroke symptoms often coincided with the onset of hypertension or a period when blood pressure was climbing. Later population studies confirmed that hypertension is extremely common in these patients, though it appears at similar rates in patients with large-artery disease, suggesting that high blood pressure may be necessary but not sufficient on its own. Diabetes also contributes to the thickening and damage of these small vessels.
High Blood Pressure, Diabetes, and Cholesterol
The major modifiable risk factors for ischemic stroke are high blood pressure, diabetes, and elevated cholesterol. They don’t cause strokes directly. Instead, they accelerate the arterial damage described above.
High blood pressure is the single most powerful driver. It damages artery walls at every level, from the large carotid arteries down to the smallest vessels deep in the brain. For people with diabetes, current guidelines recommend keeping blood pressure below 130/80 mmHg to reduce stroke risk.
Diabetes increases stroke risk through several pathways. High blood sugar damages the inner lining of blood vessels, promotes inflammation, and makes blood more prone to clotting. Studies have identified a fasting glucose level around 120 mg/dL as a threshold above which stroke risk begins to rise. Keeping long-term blood sugar (measured by HbA1c) below 7.0% is a widely used target for reducing vascular complications.
High LDL cholesterol fuels atherosclerosis, the plaque buildup that narrows arteries and produces the vulnerable plaques that break off and cause embolic strokes. For people with diabetes who haven’t had a stroke, keeping LDL below 100 mg/dL is the standard goal. For those who have already had a stroke, the target drops to below 70 mg/dL.
Less Common Causes
In younger adults especially, ischemic stroke can have causes that fall outside the usual risk factors.
Arterial Dissection
A tear in the inner wall of a carotid or vertebral artery (the arteries running through the neck) can trigger a stroke. The tear creates a flap of tissue inside the artery that disrupts blood flow and provides a surface where clots readily form. Those clots can then travel to the brain. The underlying cause is thought to be multifactorial: some people have an inherent weakness in their vessel walls that makes them more susceptible. These same individuals are more likely to have other vascular abnormalities like intracranial aneurysms or an unusually wide aortic root. Arterial dissection can follow trauma, chiropractic manipulation, or even vigorous coughing, but it also occurs spontaneously.
Patent Foramen Ovale
A patent foramen ovale, or PFO, is a small hole between the two upper chambers of the heart. It’s a remnant of fetal circulation that normally closes after birth but stays open in a significant portion of the population. In most people it causes no problems, but in certain circumstances a blood clot from the venous system (typically the legs or pelvis) can cross through the hole into the arterial circulation and travel to the brain. This is called paradoxical embolism. A PFO has been found in up to 50% of patients under 55 who have a cryptogenic stroke, far higher than in the general population. The hole can also contribute to stroke through clot formation along the septum itself or by promoting atrial arrhythmias.
Transient Ischemic Attacks as a Warning
A transient ischemic attack, or TIA, is caused by the same mechanisms as a full ischemic stroke, but the blockage resolves on its own and symptoms disappear, usually within minutes to an hour. The causes are identical: a small clot from the heart, a fragment from a carotid plaque, or temporary closure of a small vessel.
A TIA is not a minor event. It signals that the underlying cause is active and another, potentially larger, clot could form at any time. The risk of a disabling stroke after a TIA is between 2% and 17% within the first 90 days, and much of that risk is concentrated in the first hours and days. A TIA and a full stroke share the same root causes, and identifying and treating those causes after a TIA is one of the most effective ways to prevent a major stroke.