88% of all strokes are ischemic; an ischemic stroke results in a lack of, or reduced blood flow to the brain. When brain ischemia occurs, inflammatory responses are triggered in an attempt to heal the damaged tissue. However, these inflammatory responses are actually causing further tissue damage, leading to a greater amount of infarct, or dead tissue, in the brain. Reperfusion, the return of blood flow to the ischemic tissue, is the goal of most clinical therapies to treat ischemic brain injury. In spite of the benefit of returning blood to the ischemic brain, reperfusion also initiates inflammatory responses, such as the activation and recruitment of leukocytes, which may increase secondary injury to the brain. This secondary injury is called reperfusion injury.
Neutrophils are inflammatory responders to injury and disease. They are usually the first type of leukocyte to arrive at the injured site. After cerebral ischemia and reperfusion, neutrophils activate and adhere to the vascular endothelium where they contribute to cell death by producing cytotoxic substances and decreasing blood flow. Neutrophils increase injury by directly secreting deleterious substances or other inflammatory mediators. Several studies have shown that infarct volume is significantly reduced when neutrophil infiltration is inhibited.
It has been proven in experimental stroke that blocking various aspects of the inflammatory cascade reduces the amount of infarct. The problem is figuring out how to do this at the clinical level. This raises many questions on when and how to treat a patient who has had an ischemic stroke. At what point during brain ischemia and reperfusion is inflammation destructive? When is the inflammation beneficial and necessary for repair? What is the optimal time during an ischemic stroke to modulate the inflammatory responses? Clinically, the overall goal is to reduce the amount of dead tissue in the brain resulting from ischemia and the inflammatory responses so that the patient may retain as many neurological functions as possible. The greater the amount of infarct, the more neurological deficits that result. Understanding how and when these inflammatory responses play a role in stroke is essential for finding the best way to treat a stroke patient.
Dear Dana,
ReplyDeleteYou captured the essence of leukocyte (specifically, neutrophil)-mediated injury during reperfusion after a stroke. What a conundrum...giving blood back to an ischemic organ, in this case, the brain, sounds like such a good idea. It is, but those pesky neutrophils cause a little (or alot?) of damage that extends the ischemic damage. So, the bid goal is to reduce the time of ischemia AND find treatments to reduce the activated neutrophil response. To answer your question of "how soon do we treat activated neutrophil", I have an answer to that. Treatment should be at the same time as blood is returned. Our research demonstrates that activated neutrophils adhere to the blood vessels (and cause damage) the minute the blood the blood is swept back into the brain circulation. Dr. L. Ritter
FYI/Disclaimer/You probably figured it out: I am a stroke researcher here at the Univ. of Arizona and Dana works in my laboratory. She is co-author on a recent publication from our laboratory that described the neutrophil-mediated response to stroke in a murine model. Way to go, Dana! LR
ReplyDeleteI like the way you presented how stroke and inflammatory are closely related. Also, you maintained that 88% of the strokes are ischemic, meaning that the lack of oxygen in those particular tissues will trigger the inflammatory response. I was just wondering if you happened to know the other types of strokes that are representing the remaining 12%. In your blog you said reperfusion is the goal of most clinical therapies to treat ischemic brain injury. Well, to my knowledge there is no way to treat damaged cells in the brain so what’s the point of supplying dead tissues by oxygen? Is there a period of time after the stroke took place that you can bring the tissue to life again by treating ischemia in that certain period of time? Overall, thank you for such a beneficial and easily-understandable blog.
ReplyDeleteHemorrhagic stroke accounts for the other 12% (approximately) of stroke cases. This occurs when a blood vessel ruptures inside the brain, and the resultant bleeding damages the brain tissue.
ReplyDeleteReperfusion is the goal of most clinical therapies to treat ischemic brain injury. The necrosis that may occur in the brain tissue due to ischemia is irreversible, meaning that once brain cells have died, they cannot be revived. Reperfusion is still important, however, to try and prevent further brain cells from dying. The longer the ischemic period, the greater the amount of tissue death. Therefore, reperfusion must be initiated as quickly as possible in order to minimize the amount of infarct and help the patient retain as many neurological functions as possible.
You mentioned that it has been proven that blocking certain parts of the inflammatory cascade can decrease the amount of infarct. what exactly are they blocking? and have there been any problems with turning off part of the cascade that you might know of?
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