May 2007

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Children's latest research

.: Hydrocephalus gets turned on its head :.

.: Gay and lesbian teens face more bullying :.

.: One cancer, many paths :.

Joseph Madsen, MD, examines patient Peter Dee-Collins.

Hydrocephalus gets turned on its head
The neurosurgery world is abuzz with new theories about hydrocephalus—a damaging buildup of cerebrospinal fluid inside the brain that affects about one in 500 newborns, as well as many adults. A March symposium, hosted by Children's Hospital Boston neurosurgeon Joseph Madsen, MD, and sponsored by the BrainChild Foundation, drew researchers from as far away as Norway and has sparked new collaborations to develop better hydrocephalus treatments. "The meeting was pivotal," says Madsen, director of Children's Neurodynamics Lab.

Traditionally, hydrocephalus was thought to be caused by an imbalance of production and absorption of cerebrospinal fluid. The usual treatment is surgery to place a shunt—a valve that drains the excess fluid from the brain. After shunts were invented in the 1950s, researchers largely lost interest in hydrocephalus, thinking that it was solved. But shunts are not an ideal solution: They must be managed and replaced throughout life, and often cause complications and side effects like infection, obstruction and chronic headaches.

Studying the problem, Madsen and colleagues at Stony Brook University realized that the key to hydrocephalus may not be the amount of fluid in the brain, but rather the fluid's pulsing motion. These natural pulses, linked to the heartbeat, may help ensure adequate blood flow in the brain. However, the smallest blood vessels need to be buffered from the pulses to protect them from mechanical stress. Madsen and colleagues have discovered a system that does this in the normal brain, and speculate that malfunction of this system contributes to hydrocephalus. "One reason people with hydrocephalus get headaches may be that their shunts don't solve the problem of buffering the pulsations," Madsen says.

A host of symposium presentations provided support for these speculations—but also opened up completely new ways of looking at hydrocephalus—even the possibility of treating it with drugs. Judah Folkman, MD, director of Children's Vascular Biology Program, theorized that leaky blood vessels may have a role. Don Ingber, MD, PhD, also of Vascular Biology, offered insights about the role of mechanical stress in disease, and Larry Benowitz, PhD, who directs neuroscience research in Neurosurgery, outlined how, in glaucoma, mechanical stress triggers a cascade of biochemical activity that destroys key nerve cells, causing blindness. "It could be that if there's lasting damage from hydrocephalus, it's through the same pathway," says Madsen.

Michael Klagsbrun, PhD, of Vascular Biology, and Leonard Zon, MD, PhD, director of the Stem Cell Research Program, have created animal models of hydrocephalus—in mice and zebrafish, respectively—that could be used to test the new theories and perhaps drug treatments. With at least 150 patients seen for hydrocephalus each year at Children's, Madsen and colleagues are eager to move ahead.

From left, Heather Corliss, Elise Berlan, MD, and Bryn Austin, ScD.

Gay and lesbian teens face more bullying
Nearly half of adolescents identifying as lesbian or gay report having been bullied in the past year, say Elise Berlan, MD, and Bryn Austin, ScD, in Children’Äôs Division of Adolescent Medicine. They analyzed data from more than 7,500 adolescents, aged 14 to 22, involved in the national Growing Up Today Study. After adjusting for age and other factors, lesbians and gays were three to four times more likely than heterosexuals to report having been victimized. Bisexuals and those identifying as "mostly heterosexual" were twice as likely.

The researchers now plan to conduct a more detailed follow-up study looking at the health effects of bullying. "We know that sexual minorities are more likely to smoke, drink, use drugs and have eating disorders and depression," says Austin. "We suspect that social isolation, harassment, bullying and sometimes violence against these adolescents may be an explanation."

One cancer, many paths
A tumor cell is born. Will it stay tiny and dormant, like most tumors, or will it grow, spread and become life threatening? An interactive, animated feature on our Research Web site (www.childrenshospital.org/research) lets users follow cancer as it progresses and choose their own routes as it moves through as many as 14 possible stages. The feature was produced by Rick Groleau in Public Affairs and the Information Services Department, aided by Marsha Moses, PhD, and Bruce Zetter, PhD, of Vascular Biology.

:: Erin Graham, Editor :: Masthead ::

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