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 New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

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: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>