Avenues opened by new understanding of brain injury in preterm infants

A study conducted by a scientist at The University of Auckland with colleagues at the Oregon Health and Science University in the United States has resulted in findings with the potential to prevent or reverse serious disabilities in children born prematurely.

This research, performed as part of postdoctoral research at the Oregon Health and Science University’s Doernbecher Children’s Hospital and published online in the 16 January issue of Science Translational Medicine, is challenging the way paediatric neurologists and scientists think about brain injury in preterm infants. Specifically, it overturns the long-held belief that low blood flow to the developing brain causes death of neurons.

“The investigation has shown that brain injury in preterm born babies is not necessarily irreversible, as was previously thought”, says Dr Justin Dean from The University of Auckland’s Department of Physiology and Centre for Brain Research, who is first author for the study.

“Neuronal cells in the cortex of the brain play an important role in thinking or cognition. Loss of these cells can severely impact on normal brain function. It was very surprising to find that neurons were not actually killed in the preterm brain. Rather these cells did not develop or mature as they should, and they had less connections to other cells.”

“This finding has changed the way we consider the cognitive and learning disabilities that occur in preterm babies.”

“It opens new avenues for potential therapies to promote regeneration and repair of the premature brain.”

Lead investigator, Stephen Back, Professor of Paediatrics and neurology at the Oregon Health and Science University, says: “As neurologists, we thought that ischemia killed the neurons and that they were irreversibly lost from the brain. But this new data challenges that notion by showing that ischemia, or low blood flow to the brain, can alter the maturation of the neurons without causing the death of these cells.

“As a result, we can focus greater attention on developing the right interventions, at the right time early in development, to promote neurons to be more fully mature and reduce the often serious impact of preterm birth. This is a much more hopeful scenario.”

In studies using new MRI technology that allows injury to the developing brain to be identified much earlier than was previously feasible, the researchers looked at the cerebral cortex, or “thinking” part of the brain, which controls the complex tasks involved with learning, attention and social behaviours that are frequently impaired in children who survive preterm birth.

Specifically, they observed how brain injury in the cerebral cortex evolved over time and found no evidence that cells were dying or being lost. They did notice, however, that more brain cells were packed in to a smaller volume of brain tissue, which led, upon further examination, to the discovery that the brain cells were not fully mature.

Dr Dean says the findings are particularly exciting when looked at in association with a related study, published in the same online issue of Science Translational Medicine, in which investigators at the Hospital for Sick Children and the University of Toronto studied 95 premature infants using MRI.

"These researchers found similar MRI abnormalities in the cortex of preterm born babies to those observed in our experimental studies. Impaired growth of these babies was also the strongest predictor of these MRI abnormalities. This suggests that improving neonatal growth may allow normal development and growth of the cortex, which may reduce neurological deficits associated with preterm birth.”

“In New Zealand around 500 babies are born prematurely every year, and between 25 and 50 percent of children born prematurely develop deficits in behaviour, learning and cognition by school age,” says Dr Dean. “These two studies, taken together, provide important directions for further research into the early identification of at risk infants and potential therapies that may make a difference to neurological outcome for these children.”

This study, “Prenatal cerebral ischemia disrupts MRI-defined cortical microstructure through disturbances in neuronal arborization,” was supported by grants from the National Institutes of Health, National Institute of Neurological Disorders and Stroke, a Bugher Award from the American Heart Association, the March of Dimes Birth Defects Foundation, and a Heubner Family Neurobiology of Disease Postdoctoral Fellowship.