The study, which is published online in Nature Medicine by scientists from University of Michigan Medical School and the Ludwig Institute at Karolinska Institutet, is performed on mice.
However, to test the theory in humans the researchers soon will begin a clinical trial in collaboration with the Karolinska University Hospital in Stockholm, using the leukemia drug known as imatinib (Glivec®).Their recent study on mice showed that the drug greatly reduces bleeding, even if tPA wasn't given until five hours after a stroke began.
"Ten years ago our research group identified the growth factor PDGF-CC, and we are now very excited having unraveled a mechanism in the brain involving this factor", comments the Karolinska Institutet team leader, Professor Ulf Eriksson. "This finding has indeed the potential to revolutionize the treatment of stroke."
The new paper details a series of molecular and cellular experiments conducted by the Swedish and American research teams, which began collaborating after hearing of each other's work. They report that tPA apparently causes its risk of bleeding, and leakage of fluid within the brain, by accident. The culprit is tPA's tendency to act upon a protein called PDGF-CC, and the PDGF-alpha receptor that it binds to. This interaction causes the usually impervious blood-brain barrier to become porous, leading to leakage.
Imatinib, however, inhibits the PDGF-alpha receptor permitting tPA to do its main job, which is to down clots that have lodged in the brain's blood vessels. If the clots are not removed, they will cut off blood supply and eventually starving brain tissue until it begins to die.
According to the World Health Organization (WHO), clots in the brain blood vessels causes 80 percent of the 15 million strokes that occur each year worldwide. Five million people die, and 5 million more are permanently disabled, by strokes each year.
"Our findings have immediate clinical relevance, and could be applied to find new treatments that will benefit stroke patients," says senior author, Professor Daniel Lawrence at the U-M Medical School. "By better understanding how the brain regulates the permeability of the blood-brain barrier, and how tPA acts upon that system, we hope to reduce the risks and increase the time window for stroke treatment."
Funding for the study came from the National Institutes of Health, the Ludwig Institute for Cancer Research at Karolinska Institutet, the Novo Nordisk Foundation, the Swedish Research Council, the Swedish Cancer Foundation, the LeDucq Foundation and the Inga-Britt and Arne Lundberg Foundation.
Publication: 'Activation of PDGF-CC by tissue plasminogen activator impairs blood-brain barrier integrity during ischemic stroke', Enming J Su, Linda Fredriksson, Melissa Geyer, Erika Folestad, Jacqueline Cale, Johanna Andrae, Yamei Gao, Kristian Pietras, Kris Mann, Manuel Yepes, Dudley K Strickland, Christer Betsholtz, Ulf Eriksson och Daniel Lawrence Nature Medicine, AOP 22 June 2008, doi 10.1038/nm1787.For further information, please contact:
The importance of biodiversity in forests could increase due to climate change
17.11.2017 | Deutsches Zentrum für integrative Biodiversitätsforschung (iDiv) Halle-Jena-Leipzig
Win-win strategies for climate and food security
02.10.2017 | International Institute for Applied Systems Analysis (IIASA)
Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
23.11.2017 | Information Technology
23.11.2017 | Physics and Astronomy
23.11.2017 | Life Sciences