Commonly used drug offers promise for premature babies

Scientists have found evidence that the cox-2 inhibitor celecoxib, a common pain reliever used to treat arthritis, may offer a new way to reduce the risk of the most common cause of brain damage in babies born prematurely.

The work involves shoring up blood vessels in a part of the brain that in premature infants is extremely fragile and vulnerable to dangerous bleeding, which affects an estimated 12,000 children a year, leaving many permanently affected by cerebral palsy, mental retardation, and seizures.

"Stabilizing the blood vessels right before the baby is born is a tremendous opportunity to save the baby from potentially lifelong complications," said Maiken Nedergaard, M.D., Ph.D., a neuroscientist at the University of Rochester Medical Center who is presenting the results at a neuroscience meeting, Brain '07, in Osaka, Japan May 20-23.

The laboratory research was done primarily in a laboratory at New York Medical College led by neonatologist Praveen Ballabh, M.D. Ballabh's team worked with Rochester neuroscientists including Nedergaard, Steven Goldman, M.D., Ph.D., and Nanhong Lou, Ph.D. A research article describing the work appeared in the April issue of Nature Medicine, which included a cover photograph taken by the Rochester team showing the brain cells involved in the brain damage seen in some premature infants.

The research is based on extensive brain studies of infants who died prematurely as well as on findings with newborn rabbits, whose brains resemble those of premature babies in some very important ways. The medication would need to be tested rigorously in pregnant women before being considered as a treatment for their babies. But the investigators point out that celecoxib is already used widely in people, including pregnant women, making a clinical trial in people feasible.

The researchers focused on a part of the brain known in developing infants as the germinal matrix, a temporary structure that is the birthplace of all brain cells in an infant. The structure runs like a jagged coastline just below spaces in the brain called ventricles, and in premature infants it's extremely active, churning out new brain cells that migrate and settle into other parts of the brain.

"This is a very, very important part of the brain, from which neurons and glia cells migrate out to form all the layers of the brain," said Ballabh, an associate professor in the Department of Pediatrics, Cell Biology, and Anatomy at New York Medical College, and a neonatologist at Westchester Medical Center.

The germinal matrix is designed to be active until around week 36 of gestation. Then, with most of the infrastructure of the brain in place, the germinal matrix disintegrates and shrinks into a much smaller brain region known as the ventricular zone in adults.

The problem is that the germinal matrix is as fragile as it is crucial during its brief existence. While it's turning out new brain cells, it demands more oxygen and more blood flow, a demand that the body meets by building a network of temporary – and very fragile, awkward, and leaky – blood vessels.