Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Northwestern widens ’treatment window’ for brain injury and stroke

03.09.2003


In the treatment of stroke, there is currently only a three-hour "window of therapeutic opportunity" to prevent additional brain cell damage and only one medication approved to improve blood flow to oxygen-deprived neurons near the injury, thereby minimizing potentially debilitating side effects.



Now, scientists from Northwestern University report that a single injection of a chemical they created -- given up to six hours after brain injury or stroke -- protects against additional brain cell death for a week or longer. An article describing the new compound and its activity in the body appears in the September online issue of the Bioorganic and Medicinal Chemistry Letters.

The compound inhibits activity of an enzyme called death-associated protein kinase (DAPK), known to be an early player in the chain of molecular events leading to apoptosis, or programmed cell death. Earlier studies showed that levels of DAPK increase markedly prior to neuron death and that apoptosis increases rapidly hours after the onset of a stroke in laboratory models.


"Results of this study support the idea that targeting protein kinases, which function early in programmed cell death pathways, could identify new therapeutic approaches to acute brain injury," said Northwestern scientist Martin Watterson, who led the study. Watterson is John G. Searle Professor of Molecular Biology and Biochemistry, professor of molecular pharmacology and biological chemistry at the Feinberg School of Medicine and director of the Drug Discovery Program at Northwestern University.

The timing of DAPK’s increase in those early studies, coupled with its ability to initiate cell death, suggested to Watterson and co-researchers that a drug that inhibits DAPK activity might prevent or reduce neuron death in the critical period following brain injury or stroke.

The researchers created a small-molecule DAPK inhibitor based on data derived from their own earlier experiments. They had developed a quantitative assay for DAPK that subsequently helped them design methods for identifying candidate DAPK inhibitors, and later, with collaborators at Vanderbilt University, determined the three-dimensional structure of a region on the DAPK molecule that is essential to triggering programmed cell death.

While initial results with the DAPK inhibitor provide a precedent for drug discovery research in acute brain injury, Watterson explained that the compound’s molecular properties did not make it an ideal candidate for drug development. However, now that a candidate inhibitor has been identified, the researchers will use the region on the DAPK molecule as a framework and employ fragment-based, structure-assisted drug design technology to create related, or analog, inhibitors with more desirable molecular properties.

Other researchers on this study were Anastasia V. Velentza, Mark S. Wainwright, Magdalena Zasadzki, Saalida Mirzoeva, Andrew M. Schumacher and Pamela J. Focia, Feinberg School of Medicine at Northwestern University; Jacques Haiech, Universite’ Louis Pasteur, Illkirch, France; and Martin Egli, Vanderbilt University, Nashville.

Elizabeth Crown | EurekAlert!
Further information:
http://www.nwu.edu/

More articles from Health and Medicine:

nachricht Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Osaka university researchers make the slipperiest surfaces adhesive

18.10.2017 | Materials Sciences

Space radiation won't stop NASA's human exploration

18.10.2017 | Physics and Astronomy

Los Alamos researchers and supercomputers help interpret the latest LIGO findings

18.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>