Cognitive impairment in premature babies not permanent

The learning difficulties that can result from premature birth may not be inevitable. That's the exciting conclusion of two independent but complementary studies.

Together, the studies suggest that the relatively small cerebral cortex seen in many preterm babies contains a normal number of neurons despite its size ? and that these neurons could be nurtured back to health with the right postnatal care.

"For decades we thought of survivors of preterm birth as having a devastating permanent injury," says Stephen Back at the Oregon Health & Science University in Portland. The small cerebral cortex was widely assumed to reflect insufficient neurons in this part of the brain, perhaps because some of the cells are lost following the ischemia ? reduced blood flow to brain tissue ? often experienced by premature babies.

Back and colleagues decided to look at the effects of ischemia on the developing cortex in more detail. To do so they used a fetal sheep brain, as this animal model has been shown to closely match the brain of human fetuses. In a "painstaking but very accurate" process, Back's team used microscopy techniques to count the number of neurons in samples taken from fetal sheep brains that had suffered induced ischemic injury and those that had not.

Though the injured cortices had a smaller volume, Back's team was surprised to find that they had the same number of cells as uninjured cortices. "We counted the money and it was all there," says Back. "But the cells were all squished together."

Neuron 'saplings'

To get a better idea of what was going on, the researchers stained the cells and looked at their structure. Mature neurons have a tree-like structure, with dendrites extending radially from the cell like branches. The cells from the injured brain lacked these branches. "Instead of oak trees, we saw saplings," says Back.

The team then used an MRI technique that measures how water diffuses through brain tissue, called diffusion tensor imaging, to explore what effect this would have. In tissue with fully branching neurons, water diffuses randomly in all directions. In the damaged neurons, however, water diffused towards the surface of the brain ? an indication of neuron immaturity.

This explains why the cortex volume was smaller, says Back. In a normally developing brain, the cortex expands rapidly in the third trimester as the cells start to blossom. The reduced blood flow had stopped this from happening.

In a sister study, Steven Miller at the Hospital for Sick Children in Toronto, Canada, and colleagues conducted a comprehensive survey of the links between neonatal care and brain development in 95 preterm babies. "The surprising detail was that it was mostly the cerebral cortex that is influenced, not the whole brain," says Miller.

What's more, MRI scans of the premature babies when they were 32 and 40 weeks old showed the same pattern that Back's team found in their animal tissue with under-developed ? but not dead ? neurons. "There's a remarkable agreement between the two studies," says Back. "The data is spot on." Miller agrees: "We think we're seeing the same thing."

These findings could change the way we think about brain damage. "The injury is not as bleak as we used to think. It's a disorder of maturation, not of loss," says Back.

Jump start cells

Miller's study suggests that better nutrition or cognitive stimulation might be a way to promote brain growth. "It's possible to alter the development of the brain by changing the environment of an individual," says Back. "You could jump start the cells and get them developing again."

Miller's team will follow the development progress of the 95 babies to see how changes in development within the cerebral cortex relate to their cognitive development. "Our long-term hope is that improving postnatal factors will also enable us to improve outcomes," he says.

"It's a ground-breaking study," says Zolt?n Moln?r at the University of Oxford, describing Back's work. "The cells don't die, they are there ? the brain can catch up."

But Moln?r also says it is a pity that Back's team did not look at other brain regions, such as the cortical subplate, which is one of the first places that neurons are generated in the fetus.

Other than blood loss, exactly what triggers these brain cells not to mature is still unknown. And what kind of environmental stimulation would be needed to prompt neurons to mature is another open question. But we should certainly focus on neonatal care, says Moln?r, and explore how illness, nutrition, and clinical therapies affect the developing cortex.

The findings are genuinely illuminating, says David Edwards at University College London ? but he thinks that we should not be too quick to settle on underdeveloped neurons as the only explanation for reduced cortical volume. "They have room to grow, but by how much?" he says.

Journal references: Science Translational Medicine: Back's study: doi.org/j8s; Miller's study: doi.org/j8t

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