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New Treatments for Brain Injury

Cells that have been largely ignored may be the best target.
November 17, 2008

Developing new treatments for brain injury has been notoriously difficult. Perhaps, new research suggests, scientists have been targeting the wrong kind of brain cells. Two studies presented Sunday at the Society for Neurosciences conference in Washington, DC, show that astroglial cells, a type of brain cell traditionally thought to support neurons, may provide an important target for new therapies.

While some of the neural damage that accompanies traumatic brain injury, such as that caused by car accidents or explosions, results from the impact of the accident, most of it unfolds over days, weeks, and perhaps even months after the injury, triggered by a chemical cascade that, in turn, triggers inflammation and cell death. Scientists would ideally like to develop a treatment that prevents this slow degeneration, but decades of research have so far left them empty-handed.

The red-blood-cell booster hormone erythropoietin (EPO), used therapeutically to treat anemia and illegally by endurance athletes, has unexpectedly emerged as a promising candidate over the past few years. Several studies in animal models show that it can protect against the cell death that accompanies traumatic brain injury in animals. Eli Gunnarson, of the Karolinska Institute, in Sweden, has now shown that EPO can protect against the swelling in traumatic injury as well, one of the most potentially damaging consequences of both brain trauma and stroke. Gunnarson’s group found that the drug works by targeting the astroglia (also known as astrocytes), closing down a channel that normally imports water into these cells. “People have underestimated the importance of astrocytes,” says Gunnarson.

In a second study, David Meaney and his colleagues at the University of Pennsylvania, in Philadelphia, found that astroglia receive a flood of calcium right after injury, which previous research suggests is toxic to neurons. They then found a class of compounds that could block the flood by inhibiting a specific receptor on the cells’ surface, suggesting a new target for drug development.

Meaney adds that neurons may have proved a poor target for brain-injury therapies in the past because drugs that “block these receptors might also inhibit important physiological functions.” He says that the same may not be true of astroglia because of their different role in the brain.

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