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Taming the clot-buster tPA
Ted M Dawson & Valina L Dawson
Nature Medicine 2006;12(9):993-4
Studies have found that strokes treated with tissue plasminogen activator (tPA) can help dissolve blood clots
and improve outcome, but tPA can also increase the risk of hemorrhage and cause other deleterious effects.
Scientists have developed a new approach that reduces the risk of intracranial bleeding and minimizes other
deleterious effects of tPA on animal models by administering a hexapeptide (EEIIMD) that spans a region of
plasminogen activator inhibitor type (PAI-1) which interferes with a part of tPA signaling that is not involved in
clot-busting activity.
http://www.nature.com/nm/journal/v12/n9/full/nm0906-993.html
Neutralizing the neurotoxic effects of exogenous and endogenous tPA
William M Armstead, Taher Nassar, Saed Akkawi, Douglas H Smith, Xiao-Han Chen, Douglas B Cines & Abd Al-Roof Higazi
Nature Neuroscience 9, 1150 - 1155 (2006); doi: 10.1038/nn1757
Published online August 27 2006
The clinical use of tissue-type plasminogen activator (tPA) in the treatment of stroke is profoundly constrained
by its serious side effects. We report that the deleterious effects of tPA on cerebral edema and intracranial
bleeding are separable from its fibrinolytic activity and can be neutralized. A hexapeptide (EEIIMD) corresponding
to amino acids 350–355 of plasminogen activator inhibitor type 1 (PAI-1) abolished the tPA-induced increase in infarct size and
intracranial bleeding in both mechanical and embolic models of stroke in rats, and reduced brain edema and neuronal loss
after traumatic brain injury in pigs. These experiments suggest mechanisms to reduce the neurotoxic effects of tPA without
compromising its fibrinolytic activity, through the use of selective antagonists and new tPA formulations.
http://www.nature.com/neuro/journal/v9/n9/abs/nn1757.html
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