New Insights On Sequence of Cell Death After Brain Injury: Understanding Cellular Events After Brain Trauma Could Lead To Better Therapies

l patterns of programmed cell death in the injured rat brains, at post-injury intervals of 12 hours to two months. The protracted time frame is unique to this study. Not all regions of the brain responded similarly. Early on, much of the programmed cell death occurred near the surface of the brain where the injury occurred. Then a progressive wave of cell death extended deeper into the brain, ending up in the thalamus, the region responsible for coordinating motor function.

In addition to the clear implications for treating brain injuries, this study adds to the growing basic knowledge of programmed cell death, an area of active research on many fronts. Apoptosis involves the expression of cell-death genes inside a particular cell. For example, apoptotic genetic programs cause some types of cancer cells to die.

"But in the brain, programmed cell death technically only occurs in developing brain cells in utero," explains McIntosh. "Cell death genes are expressed during development because there's an enormous amount of cellular redundancy in the fetal brain. The programmed cell death genes encode proteins that kill superfluous cells. Those genes get downregulated after birth and are not expressed, to our knowledge, in normal adults. Hence, one of the interesting things about this paper is that it documents that these genes are reactivated after a traumatic injury. Unfortunately, this is a destructive pathway that kills useful adult cells."

Penn colleagues John Q. Trojanowski, MD, PhD, professor of pathology and laboratory medicine, and Ramesh Raghupathi, PhD, research assistant professor in neurosurgery, also collaborated on the study. This research was supported by grants from the National Institutes of Health and the Veterans Administration.

Editor's Note: Dr. McIntosh can be reached at 215-573-3156 or mcintosh@eniac.seas.upenn.edu

The University of Pennsylvania Medical Cente

Contact: Karen Young Kreeger
University of Pennsylvania School of Medicine

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