Improving Brain Cell Survival After Trauma

Researchers from the Howard Florey Institute at the University of Melbourne (Australia) discovered that this naturally occurring protein, called BP5, is produced more than usual in brain cells after they have experienced traumatic injury. The researchers used serial analysis of gene expression (SAGE) to identify 50,000 sequence tags, representing 18,000 expressed genes in the cortex two hours after traumatic brain injury.

The SAGE data were validated on mice, and were confirmed for a subset of genes using in situ hybridization and immunocytochemistry on brain sections. While the majority of the genes examined showed a downward trend in expression over time, overexpression of BP5 in cultured cortical neurons increased the number of surviving neurons after gene transfection and growth factor starvation, compared with the control transfections. The study was published in the July 5, 2006, issue of the Journal of Neuroscience.

"BP5 works by using the cell's waste disposal system to flush away toxic and damaged proteins produced after injury, which appears to tip the balance towards nerve cell survival, instead of death,” said lead author Professor Seong-Seng Tan. "BP5's pattern of expression indicates that it allows neurons to survive in a stressed environment.”

The research is the first to show that this mechanism can be fruitfully manipulated to prevent brain cells from dying. The next challenge, the researchers say, is to understand how BP5 performs it neuron-saving function and develop drugs that can do the same thing, so they can help to save as many neurons as possible in patients suffering brain injury. Such a drug would limit damage to the brain right after the injury, as well as the subsequent few days when injured nerves release "suicide factors” that cause surrounding healthy neurons to die en masse.



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Howard Florey Institute