Brain Terrain Change

5 August 2002 (All day)

Like a double-edged sword, radiation therapy for brain cancer wipes out tumors but sometimes causes cognitive decline as well. Now researchers have found that, in rat brains, the treatment prevents new neurons from growing. Further findings suggest that dampening the brain's inflammatory response to radiation therapy may help avert such damage.

To destroy brain tumors, neurosurgeons give patients a strong dose of radiation that's supposed to kill the fastest growing cells--those in the tumor--while leaving slow-growing neurons alone. Years later, however, patients cured of brain cancer often lose their ability to make new memories. Researchers suspected that radiation therapy damages the stem cells that give rise to new neurons, which are concentrated in the hippocampus, a brain region necessary for storing memories.

To determine the effects of radiation, a team led by neuroscientist Theo Palmer at Stanford University gave rats a dose of radiation approximating the dose given to patients. The number of new neurons created by stem cells in the irradiated brains fell by 97% in 2 months, the researchers report in the 5 August issue of Nature Medicine. To test whether radiation harmed the stem cells themselves or the hippocampus in which they reside, they cultured a petri dish full of stem cells from irradiated brains. The cells generated neurons as readily as nonirradiated cells. However, when the team put fresh stem cells into the brains of previously irradiated rats, the cells no longer pumped out neurons, showing that radiation damages the hippocampus. The harm may be caused by long-lasting inflammation, the team found: The brain's immune system cells were about 25% more plentiful in irradiated rats, even 2 months later. Palmer suggests that inflammation blockers, including "a very rare drug called aspirin," might protect the brain.

Neurobiologist Evan Snyder at Harvard Medical School in Boston says the work is both good news and bad news for those hoping to use stem cells to cure both radiation-induced damage and brain disorders such as Parkinson's disease. Researchers can't just throw stem cells into "unfertile terrain" in a brain and expect them to regrow neurons, he says. But "when we understand what the terrain is like, we can make the terrain more hospitable."

Related sites
Theo Palmer's site at Stanford University Medical School

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