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 personality factor: How to foster the sharing of research data
06.09.2017 | ZBW – Leibniz-Informationszentrum Wirtschaft
Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung
At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.
Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
25.09.2017 | Power and Electrical Engineering
25.09.2017 | Health and Medicine
25.09.2017 | Physics and Astronomy