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For 20 years nothing has changed but the rising frustration of neonatologists, helpless to prevent physical and mental damage—even death—to healthy infants starved for oxygen to the brain.

Nothing's changed, until now.

Researchers have found that cooling the brain of an asphyxiated animal can slow or temporarily arrest the cell death process and allow the cells to gather resources they need to stay alive. Now, an MUSC study, soon to become a national multicenter study, is going to determine whether moderate hypothermia can decrease brain injury in asphyxiated newborn infants.

Dorothea Eicher, M.D., one of three MUSC neonatologists on the study team, explained that there are any number of reasons oxygen is cut off to cells in the brain. In many cases, an infant's placenta is torn from the uterus wall in birth. Sometimes the umbilical cord becomes tangled. These infants have a 60 to 100 percent chance of dying.

Other causes of asphyxia are brain injury, cerebral palsy, mental retardation, seizures, speech and hearing problems, or other mental disability.

“Parents expect no problems. The pregnancy is normal and full-term, and then suddenly there's injury to the brain. It's devastating,” Eicher said.

Research into the molecular and cellular mechanisms of cell death from asphyxia indicates a core of neurons dies quickly. But many more of these brain cells struggle for days and weeks after. It's this secondary cell death, called apoptosis, that Eicher and the study team hope to prevent.

The idea of cooling to slow cell functions and prevent damage from oxygen deprivation, a treatment called hypothermia, is nothing new. Cardio-thoracic surgeons do it all the time in open heart surgery to prevent damage to heart and brain cells.

“But does it work after the period of insult?” Eicher asks. Also, how effective will cooling an asphyxiated newborn be? How much time can elapse after the injury? What is the optimum cooling temperature? How long should it continue?

Eicher said that animal studies and hypothermia treatments on adult humans with head trauma have shown improvement even if delayed several hours after the injury. “But there's a time limit. The closer to the injury you start treatment, the more neurons you save.”

When neurons in the brain become oxygen-starved, a cascade of inflammatory biochemical reactions to the insult make cell death more likely. Inflammation causes the cell to draw on its supply of ATP (adenosine triphosphate), a basic high-energy molecule essential for cell function. Once the cell's energy source is depleted, the cell begins to die.

“Hypothermia preserves ATP in the struggling cell,” Eicher said. “We don't know how long to continue the cooling and we don't know what the side effects are.” She said that as MUSC and participating medical centers study hypothermia in preventing cell death from asphyxia, other centers are working on drugs to be administered in conjunction with the treatment.

“We're hopeful for the future,” Eicher said, indicating that the preliminary data has shown better-than-expected cognitive and language outcomes in patients who receive hypothermia treatments.

“Actually, it can't get much worse than what we've been able to do in the past.”

Conducting the study are: neonatologists Dorothea Eicher, M.D.; Carol Wagner, M.D.; Lakshmi Katikaneni, M.D.; epidemiologist Tom Hulsey, Sc.D.; and biochemist John Baatz, Ph.D.