Children's National Health System

Study Targets NEUROSCIENCE 9 IN AN ARTICLE recently published in Nature, a team led by Vittorio Gallo, PhD, Director of the Center for Neuroscience Research at Children's National, provides direct evidence that targeting specific receptors in white matter cells a er brain injury promotes cellular and functional recovery. In the United States, some 500,000 babies are born prematurely each year, with about 2 percent of them born at less then 32 weeks gestation. Up to 90 percent of these children survive, but they o en suffer a number of abnormalities, including underdeveloped lungs. Insufficient gas exchange in the lungs leads to hypoxia, which in turn contributes to WMI. No treatment currently exists to improve function in these infants once injury occurs. During normal fetal and postnatal development, oligodendrocytes (myelin-producing cells in white matter) arise from oligodendrocyte progenitor cells (OPCs), which undergo a complex maturation process controlled by a number of growth factors that promote cellular proliferation and differentiation. In premature infants, hypoxia prevents OPCs from maturing properly, and the cells begin to die. Without sufficient myelin, the brain cannot process nerve impulses effectively, leading to significant delays in the development of sensorimotor skills and cognition. "We have only recently begun to understand how hypoxia and related brain injury affect white matter development and myelination in the developing brain," Dr. Gallo says. "We knew from previous research that the epidermal growth factor receptor [EGFR] plays a significant role in the maturation of OPCs. In this study, we wanted to see if enhanced EGFR signaling could stimulate the OPCs to develop normally." "Using a rodent model of premature brain injury, we administered EGF intranasally," says Joseph Scafidi, DO, pediatric neurologist at Children's National and the study's lead author. "A er treatment, the selectively targeted OPCs were identical to normal, healthy oligodendrocytes." Due to the limited duration of the OPCs' plasticity response, there is a very narrow window of intervention opportunity. "Treatment must be administered within a week a er injury," Dr. Gallo says. "A er that, there is no effect." While the team's findings demonstrate that the treatment is clinically feasible and potentially applicable to children with WMI, Dr. Gallo cautions that more research is needed to develop safe and effective therapeutic approaches. "This study highlights the importance of the brain's plasticity response," Dr. Gallo says. "Researchers need to take full advantage of that response for therapeutic purposes." White matter injury (WMI), one of the most common consequences of premature birth, can produce long-term neurodevelopmental deficits. A new study by researchers at Children's National Health System points the way toward a potential treatment. To read the study in Nature, visit www.ChildrensNational.org/ Nature. Bain Injury NEONATAL BY JONELLE TODD

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