Periventricular leukomalacia

Halting brain injury in newborns

The increasing number of in vitro fertilizations and multiple gestations has resulted in the birth of many more premature, very-low-birthweight infants in the United States. Thanks to medical advances, survival of these frail infants has increased from about 20 percent, 15 years ago, to nearly 90 percent today. But up to 35% of children who survive extreme prematurity are left with long-term complications, including PVL, which can lead to cognitive/behavioral deficits and cerebral palsy. In fact, about half of all new cases of cerebral palsy occur in survivors of prematurity.

Since PVL can't be reversed, a multidisciplinary team of Children's researchers is trying to find ways to prevent the brain injury. They meet weekly to exchange data from MRI scans of infants' brains, autopsies of brains from non-surviving infants, laboratory studies and animal studies that simulate human PVL and test possible interventions.

During the past decade, our researchers have documented a complex web of insults sustained by premature babies' brain cells, particularly the cells that form the brain's white matter, known as oligodendrocytes. Hypoxia-ischemia, a compromise of the brain's blood and oxygen supply, is often the trigger. Not only are preemies at high risk for hypoxia-ischemia, but their immature oligodendrocytes are exquisitely vulnerable to hypoxic-ischemic injury because of the developing cells' unique biology.

Now, Children's researchers have demonstrated that an existing Alzheimer's drug, memantine, can reduce white-matter injury after a hypoxic-ischemic episode. Although the study involved a rat model of cerebral palsy and brain injury in premature infants, the findings may provide the basis for a protective therapy for preterm babies.  The next step is to evaluate potential safety risks of memantine in premature newborns. Eventually, Children's researchers hope to conduct a clinical trial in premature infants at risk for PVL. "The hope is that we could intervene with the development of progressive brain injury, in order to prevent outcomes like cerebral palsy and cognitive impairment," says one of the researchers, neurologist Frances Jensen, MD.