In one of the lay articles posted, it mentioned a treatment for strokes called tPA, or tissue plasminogen activator. Out of curiosity, I did some more research to find out more about it.
tPA is a serine protease that converts the proenzyme plasminogen to plasmin, which is an enzyme that breaks down the clotting factor fibrin. When fibrin is inactivated, the clots that normally cause the occlusion of blood flow in the cerebral blood vessels are broken down and the risk is minimized considerably. Like the article stated, the tPA must be administered intravenously within three hours of the initial symptoms of a stroke (in this case, it treats ischemic stroke which constitute about 80% of all strokes) in order to be used to its full potential and possibly prevent the serious long-term effects of ischemic stroke. A major issue surrounding the usage of tPA is that due to this short time period of effectiveness, only a small fraction of ischemic stroke patients are able to put it to use, approximately 3%.
But due to advances in imaging technology, researchers are beginning to find out that there are still some advantages to administering the tPA up to eight hours after the initial symptoms. The reason for this is that the neurons that are damaged by the lack of blood flow may not all be dead in this three hour time period. Newer CT scans and MRI's can now show us which of the affected neural tissue is dead so we can see if it is still beneficial to inject the tPA to salvage some of the tissue. And just as importantly, these scans can also tell us which patients are more susceptible to bleeding when given tPA; a problem that prevents the treatment for some patients even within the initially determined three-hour time period.
These advances in the research of tPA are very beneficial to the well-being of stroke patients, and hopefully researchers will continue to build upon the treatment methods for strokes.
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Very interesting! Thanks!! I wanted to add that there is evidence that tPA has anti-inflammatory effects that are separate from the fibrinolytic effects it's well known for. This might also be a compelling reason to administer tPA after the 3 hour window.
Stringer et al. Plasminogen Activator (tPA) inhibits human neutrophil superoxide anion production in vitro.
Inflammation, Vol. 21(1) 1997
Given that no other effective therapy exists for ischemic stroke,TPA is extremely important when treating patients but a study was found in 1995 that showed TPA may increase the risk for a brain hemorrage months after the stroke occurs. so i would like to see the improvement of TPA or at least another alternative treatment that could be used even after the three hour window. i hope they hurry up with this. There has even been research that shows controlling infiltration of leukocytes into the brain could be a possible treatment in the future.
Great summary of the use of tPA in the treatment of ischemic stroke! In addition to intravenous tPA administration for those patients who do fall inside of the controversial three hour window, there are a number of interventional radiologists in the Denver area who are performing intra-arterial thrombolysis.
During this procedure a catheter is threaded, often through access of a femoral artery, into the cerebral arteries and, with angiography, to the exact location of the clot. Various mechanical devices, some that look like a corkscrew, can be used to advance into the clot along with an infusion at the site of local tPA. This avoids the bleeding risks of systemic tPA administration, broadens the available window for treatment, and allows for visualization of the progress of the procedure. A dramatic picture representation of the before and after effects of this procedure can be seen at http://www.thecni.org/neuroradiology.htm.
There certainly seems to be progress to be made in this arena of medicine, given that stroke remains the third leading cause of death in the U.S. behind heart disease and cancer, and a leading cause of long-term disability (http://www.strokecenter.org/patients/stats.htm). These new therapies seem very promising, although difficult to find and provide given how few providers are trained in them!
are current methods to amplify the activation of tpa cascades worth looking into?
Marilyns - How do you control the infiltration of leukocytes and how quickly do you have to do this?
Jessicag - Thanks for telling us about intra-arterial thrombolysis.
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