Research
Shrinking the Effects of Radiation

When former Stanford medical student, and now resident Michelle Monje, M.D., Ph.D., did a clinical rotation in pediatric neurooncology, she was struck by a grim fact of radiation therapy. "In treating children's brain cancer, we damage their brains," she says. Monje found herself haunted by the plight of kids who beat cancer only to wrestle with impaired thinking for the rest of their lives.

She couldn't stop thinking about those kids in the clinic and wondering why their cognitive damage never healed, even decades after radiation therapy ended. Looking at MRI scans of irradiated brains, she was startled to find none of the broken blood vessels or other gross physical injuries long presumed to result from cranial radiation.

Michelle Monje, M.D., Ph.D., and Theo Palmer, Ph.D., have found that radiation therapy causes inflammation of the hippocampus, which often leads to cognitive impairment in children undergoing treatment for brain cancer.

The more she thought about it, the less sense it made. Where was the damage, and how could it persist? Monje turned to lab research to pin down the problem—and her investigations pointed toward a possible solution.

Working in the laboratory of Theo Palmer, Ph.D., assistant professor of neurosurgery, she studied the brains of irradiated mice, examining the hippocampus, a center of memory and learning. Radiation, she discovered, altered brain function at the most basic level, suppressing the proliferation of hippocampal stem cells, which would otherwise form new neurons to replenish damaged regions.

Monje and Palmer went on to discover that the culprit was inflammation. Radiation-induced inflammation in the mouse hippocampus blocked the chemical signals that would normally tell the stem cells to generate fresh troops—inflammation, in other words, muffled the emergency call.

This new understanding opened a bright possibility. Protecting children's cognitive abilities during and after radiation treatment might theoretically be as simple as reducing inflammation, possibly with common antiinflammatory drugs. Further research in mice has supported that hope, but additional research is needed before it can be applied to humans. Nonetheless, Monje and Palmer are optimistic that future physicians won't have to make a devil's bargain, saving children's lives at the price of their cognitive abilities.