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Ischemic Stroke – Cause – Treatment – Prognosis

Ischemic Stroke – Ischemic Core – Ischemic Penumbra – Apoptosis – Thrombolytic Therapy

Ischemic Stroke

First of all, forget what I said about brain cell death in the stroke home page. It is true that neurons (nerve cells) die within minutes after oxygen and/or glucose supply are completely shut down. “Completely” is the key factor. Complete lack of circulation (like in cardiac arrest) does cause brain death within minutes. In strokes, however, circulation is affected in a specific blood vessel distribution rather than in all of them.

Let’s imagine that someone decides to starve to death and survives for 28 days. Someone else eats exactly half of the essential amount of food and survives for a year or even longer. Kind of cruel comparison, but this is exactly what is happening to nerve cells in the brain during stroke.

Neuron survival time in the brain during stroke depends on two major factors. They are severity of blood supply compromise and the duration of blood supply shortage.

Rapid fall in blood supply to the brain tissue between 50% and 30% will produce symptoms of a stroke even if the cells are still alive. Restoration of circulation returns nerve cells function back to normal.
Cutting circulation below 30% will cause nerve cell death and permanent loss of the brain normal function, providing this shortage lasts long enough.

Based on animal experiments, complete occlusion of middle cerebral artery for 30 minutes does not produce any permanent damage even with minimal flow (below 5mL/100g/min). Low circulation of 5mL/100g/min causes stroke in 2 hours. Cerebral blood flow of 12mL/100g/min produces stroke in 3 hours. Flow above 18 mL/100/min never leads to stroke.
I hope you’ve got the point.

Ischemic Core and Ischemic Penumbra

Ischemic stroke starts with some brain artery blockage. Let’s take the Left Middle Cerebral Artery (MCA) as an example. Within minutes the following symptoms will develop: loss of speech, weakness and numbness on the right side, calculation and reading problems, difficulty looking to the right, and right visual field cut.

As you already know, nerve cells die within minutes in case of complete lack of circulation. This is the fate of the nerve cells in the center of the brain portion supplied by MCA. This area is called an ischemic core.
The rest of the MCA territory is called an Ischemic Penumbra. Even though a large portion of the brain is not functioning, only a small central portion of the brain tissue dies immediately. The rest of neurons are just starving and will likely survive once circulation is restored; the further away from the core, the better the circulation, the longer the survival time.

The outer portion of the ischemic penumbra gets some blood supply from the neighboring areas; the ischemic core gets the least support from the neighbors. It is not hard to guess, that the ischemic core is gradually expanding, since more and more cells fail to survive. Return of normal circulation will revive at least some of the penumbra cells, but the core neurons cannot be resurrected.

This is the whole idea of the modern acute stroke management. Early aggressive treatment with restoration of the blood flow may bring most of the lost functions back, leaving only some residual weakness on the right side.

Causes of Neuron Death in Stroke

Nerve cells, or neurons, have very active metabolism. Lack of energy supply rapidly leads to loss of normal function and inability to maintain the appropriate cell composition. Neurons swell and die. Other brain cells follow the same fate shortly thereafter.

Tissue inflammation and swelling lead to even more local blood circulation problems, which enlarges the damaged area of the brain. This is what happens in the ischemic core described above.

More fortunate penumbra cells don’t die right away. They stay in half alive and half dead state for some time. Since they are not dead yet, it feels like they will come back, once the blood flow is restored.

Unfortunately, it’s not that simple. Nerve cells, as any other cells in our bodies are capable of “suicide”. There is a special chain of events called apoptosis. Apoptosis is a programmed cell death. Apoptosis is intended for sick cells to die and disintegrate in an organized manner. The benefit is lack on inflammation in the area, which might damage the neighboring cells. Basically, sick cells commit suicide in order to protect the neighbors.

Some cells in the stroke penumbra die by apoptosis. Even though they survive shortage of energy supply, the damage is severe enough to trigger this mechanism of programmed cell death. Once it starts, there is no way to stop it.

Rational for the Urgent Stroke Treatment

The only known effective treatment in acute stroke is restoration of the blood flow. It can be done with thrombolytic therapy. Another option is mechanical removal of the blood clot with special endovascular equipment. They are meant to restore the flow in the occluded blood vessel. The sooner it is done, the less nerve cells die, the better the prognosis.

No proven effective treatment for the brain tissue protection from apoptosis or other secondary damage is available at this point.

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