Funding outcome

The brain depends on a constant supply of oxygen to meet its energy needs. If this supply fails for even a few minutes permanent brain damage or death can result. Some infants born prematurely are at risk because they suffer from apnea of prematurity, a condition where breathing slows or stops (apnea) for short periods and oxygen levels fall. Unstable breathing reflects that the brain circuits that produce breathing are immature. Reductions in oxygen levels during these periods of apnea trigger an adaptive increase in breathing. However, if this increase does not immediately restore oxygen levels, the brain becomes hypoxic and the initial hypoxia-induced increase in ventilation is followed by a secondary phase where breathing is depressed, falling below baseline and becoming potentially fatal in premature infants who suffer from apnea of prematurity. In many infants, the respiratory stimulant caffeine is used to reduce these apneas and the respiratory depression. However, ~20% of infants do not respond to caffeine, so alternate treatments are required. Our previous research has shown that hypoxia causes the release of ATP in the brain areas that generate breathing, which stimulates breathing and reduces this hypoxic inhibition of breathing. The objective of this study is to determine how ATP acts in the brain to increase breathing. We will isolate slices of brainstem that generate breathing in a dish and use drugs to identify the ion channels responsible for the excitation of breathing by ATP. These data will guide development of more targeted, efficacious treatments for apnea of prematurity.