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New understanding about mechanism for cell death after stroke leads to possible therapy
Date:11/22/2009

Scientists at the Brain Research Centre, a partnership of the University of British Columbia Faculty of Medicine and Vancouver Coastal Health Research Institute, have uncovered new information about the mechanism by which brain cells die following a stroke, as well as a possible way to mitigate that damage. The results of the study were recently published online in Nature Medicine.

Following a stroke, many brain cells continue to die even after blood flow has been restored. Researchers have long known this is due to a complicated cascade of cellular messages that lead to the "self-destruction" and death of brain cells.

The team of Brain Research Centre scientists discovered that, in animal models, the over-activation of NMDA receptorsspecial receptors on the surface of brain cellsactivates another protein, called SREBP-1, which subsequently causes cell death. SREBP-1 is found naturally in cells throughout the body and is involved with cholesterol and other fat production.

NMDA receptors control the movement of calcium in and out of brain cells, which is necessary for normal brain function. However, following a stroke, levels of glutamatethe most abundant chemical messenger in the brainrise rapidly in cells, leading to over-activation of NMDA receptors, an excess of calcium entering cells, and the onset of cell death.

The researchers found that under normal conditions, SREBP-1 is largely kept in an inactive form by a protein known as Insig-1. After a stroke, over-activation of NMDA receptors leads to a rapid degradation of Insig-1, which increases the level of active form of SREBP-1.

"How over-activation of NMDA receptors caused cell death after a stroke has been a mystery," says Dr. Yu Tian Wang, co-lead on the study, a Professor in the UBC Division of Neurology, and the Heart and Stroke Foundation of BC & Yukon Chair in Stroke Research. "We found that SREBP-1 was one of the missing key players in that proces
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Contact: Melissa Ashman
mashman@brain.ubc.ca
604-827-3396
University of British Columbia
Source:Eurekalert

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