August 2001

From University of Pennsylvania

Neuron by neuron, Penn researchers study brain cells' attempts to heal themselves after severe injuries

PHILADELPHIA – Researchers at the University of Pennsylvania have won a $3.1 million bioengineering research grant to study brain injuries at a level of detail never before attained. The team, lead by Penn bioengineer David F. Meaney, will detect the genes and proteins altered in single neurons in the brain to better understand the cells’ responses to contusions and other forms of brain trauma.

The five-year grant comes from the National Institute of Child Health and Human Development, part of the National Institutes of Health. The study’s efforts to better understand brain injury at a cellular and molecular level could lead researchers to new medications and treatments for victims of brain injuries.

The Penn team will focus initially on contusions, bruises to the brain surface that often occur with skull fractures. These injuries are often localized in regions along the surface of the brain and can result in problems with the brain’s ability to process data and sensory input.

Penn investigators will examine the response of individual neurons both within and alongside areas of contusion in the brain, searching for patterns of genes and associated proteins that are activated or suppressed following an injury. For each neuron studied, researchers will compare the activated genes and protein levels to the mechanical stress experienced by the neuron at the moment of injury.

"In a sense, we want to ‘listen’ to injured neurons by looking at the genes and proteins that are preferentially expressed in these cells," said Meaney, an associate professor of bioengineering at Penn. "We’re hoping the response of these cells can give us a better idea of how to treat such injuries."

While many drugs have proven effective in animal trials, there are relatively few successful pharmaceuticals for treating human brain injuries. "Drugs for treating brain injuries need to be incredibly specific," Meaney said.

The difficulty of developing therapies for brain injuries is complicated by the fact that such injuries tend to be highly heterogeneous, with similar trauma leaving very different injuries in different individuals. Damage from a single blow to the head can be widely scattered throughout the brain, leading to injuries that can be very difficult to predict.

Meaney said that the NICHD-supported work might point researchers toward a "cocktail therapy" approach to treat the broad array of damage that occurs when the brain is injured. In addition, the mechanical sensitivity of different genes in neurons can yield unprecedented insight into the exact mechanical conditions that can cause injury in humans.

The grant to Meaney is part of NICHD’s bioengineering research partnership program, which encourages collaborative research efforts involving different universities or various research groups at a single institution. Meaney’s colleagues on the study are primarily from Penn, and include Susan S. Margulies, associate professor of bioengineering; James H. Eberwine, professor of pharmacology and associate professor of psychiatry; Tracy K. McIntosh, professor of neurosurgery; Chris Stoeckert, director of Penn’s Computational Biology Laboratories; Ramesh Raghupathi, research assistant professor of neurosurgery; Kathryn E. Saatman, research assistant professor of neurosurgery; M. Sean Grady, professor and chair of neurosurgery; and David I. Graham, a neuropathologist at the University of Glasgow.












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