Study uncovers new contributor to brain damage, suggesting novel d...( St. Louis Feb. 23 2001 Resear...)

St. Louis, Feb. 23, 2001 Researchers have identified a protein that plays an important role in neonatal brain injury. The protein, clusterin, also might contribute to adult brain damagefor example after spinal cord injury and stroke.

The results appear in the March issue of Nature Medicine. The first author is Byung Hee Han, M.D., research associate in neurology at Washington University School of Medicine in St. Louis. David M. Holtzman, M.D., an associate professor of neurology and of molecular biology and pharmacology, led the research team.

Blockage of blood flow to the brain before or during birth can temporarily deprive the brain of oxygen and other nutrients, as happens when an adult has a stroke. Without a continuous supply of oxygen, some brain cells die or are damaged, causing hypoxic-ischemic (H-I) injury. The outcome may be long-term cognitive difficulties, seizures and motor problems, as in cerebral palsy.

Scientists know of two main types of cell death, each triggered by a different cascade of biological events. In apoptosis, cells shrink and die. In necrosis, cells swell and burst.

Apoptosis accounts for about half of the cell death that occurs after H-I injury to the developing brain. Researchers have identified several ways to block apoptosis and thereby lessen brain deterioration.

Necrosis might account for the other half of brain injury after prenatal or perinatal brain trauma. It also might account for most of the cell death after adult brain injury. But because scientists have not identified all the key components of the necrosis pathway, it has been difficult to intervene to prevent it from killing cells.

To identify the main factors that contribute to the aftereffects of decreased oxygen and blood flow to the brain in newborns, Holtzmans team first examined a mouse model of cerebral palsy that mimics the effects of H-I injury. They found that an enzyme called caspase-3 became highly active in the brain cells of
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Contact: Gila Reckess
reckessg@msnotes.wustl.edu
314-286-0109
Washington University School of Medicine
27-Feb-2001