A Brain Breakthrough

Stephen Back, M.D., Ph.D., (far right) and members of his lab

Doernbecher scientists are finding new ways to reawaken damaged brain cells – and improve the quality of life for babies born too soon.

Stephen A. Back, M.D., Ph.D., is a Harvard-trained physician with prestigious international awards under his belt – but he aspires to be a repairman. Seated beside the window in his office at OHSU Doernbecher’s Papé Family Pediatric Research Institute, Back gestured across the OHSU campus. “Over at the Knight Cancer Institute, they’re going to cure cancer,” he said. “Right here, we’re going to repair the brain.”

It’s an ambition that would have seemed outrageous just a few years ago when the prevailing wisdom held that damaged brain tissue was a lost cause, unable to heal or regenerate. But today, with philanthropic investment, Back’s goal of repairing the injured brain is within reach thanks to a startling discovery that offers new hope for the most vulnerable patients of all – premature infants.

In the Doernbecher neonatal intensive care unit, the smallest premature infants weigh as little as two pounds. As head of the division of neonatology, Robert Schelonka, M.D., is responsible for giving these fragile newborns the best possible beginning. Many will face the debilitating consequences of low blood flow and low oxygen flow to the developing brain. “We know that premature babies are at high risk for cerebral palsy as well as learning and developmental disorders. That’s the reality,” Schelonka said. “The question is, at the time of injury – or even after that – is there an opportunity for us to intervene before the process is irreversible?”

The answer may come from Dr. Back, who has spent nearly 20 years researching the infant brain. “We used to think of brain injury as a destructive lesion with no hope of repair,” said Back. “We thought that the neurons were killed and that they were irreversibly lost.” In fact, grey matter in the brains of pre-term infants is shrunken – and it was long thought that the smaller volume of grey matter meant fewer brain cells. But Back and his team made a surprising discovery. “They’re all there,” he said. “We counted.” 


A tree in winter

Thanks to powerful new magnetic resonance imaging (MRI) technology, the team was able to see injury to the developing brain much earlier than previously feasible. They looked at the cerebral cortex, or “thinking” part of the brain that controls the complex tasks involved with learning, attention and social behaviors that are frequently impaired in children who survive pre-term birth. The scientists observed how brain injury in the cerebral cortex of fetal sheep evolved over one month, and found no evidence that cells were dying or being lost. They did notice, however, that more brain cells were crowded into a smaller volume of tissue. Less grey matter, it turned out, means smaller cells more tightly packed.

“To examine these individual cells,” said Back, “we took a great leap back into the 19th century.” A study that began with MRI equipment at OHSU powerful enough to pull cars off Portland’s Fremont Bridge progressed with a technique that dates to 1873, when a stain was invented that allowed scientists to observe neurons for the first time. A healthy neuron looks like a tree, with a tangle of tendrils branching outward like roots and a crown. In injured brains, Back saw cells that looked like a tree in winter, with no new growth. The neurons had stubby limbs and meager roots. “What we see is that injured cells are not maturing,” said Back. The cells are not dead, they’re stuck in a state of arrested development.


Forming new connections

This revelation caused a ripple of excitement throughout the field of neurology – and in the halls of Doernbecher’s NICU. “This means there is hope,” said Schelonka. “We might be able to intervene to influence the further development of cells in the brain.”

That aim will guide Back’s future research. The ultimate goal is to translate scientific discoveries from the lab to the bedside by finding the best ways to stimulate the brain to make new connections. Back already has some ideas. “When grandma has a stroke, she goes to rehab,” he said. “Preemie rehab is still in the realm of research – we don’t know when to start, how to do it, or for how long. But this is the way forward. We know the brain can repair itself.”

Rehabilitation is one of many possibilities, including drugs and other interventions – all of which would be aided by earlier detection of brain injuries in infants. What’s the best way to reawaken damaged brain cells? There is no good answer yet. “First we need to find out – where else does injury occur?” said Back. “Is this happening throughout the brain? We need an army just to map that out.”

Philanthropic support can help assemble and equip that army. And OHSU is the place to launch the campaign.

This research has the potential to improve quality of life for the roughly 65,000 pre-term infants born in the U.S. every year. “It’s important for us to work as fast and as hard as we can when the stars are aligned,” said Back. “This is the institution that is going to be the leader in brain repair.”