Why low oxygen levels soon after birth may raise risk for learning and behavioral disorders

"We found that chronic hypoxia is a state of neuroinflammation in the developing brain," said Lakshmi Raman, MD, a researcher involved in the work from the Department of Pediatrics at the University of Texas Southwestern Medical Center in Dallas, Texas. "Therefore, developing therapies to mitigate potentially detrimental inflammation may help reduce brain injury in infants exposed to chronic hypoxia and at-risk for developmental delay."

Scientists exposed experimental groups of mice to low oxygen from days three through 28 after birth. Control mice were exposed to normal oxygen levels (21% oxygen, i.e., room air). Researches studied brain development when exposed to low oxygen through multiple methods, including quantifying myelin protein, the number of myelin-producing cells, called oligodendrocytes, total brain inflammation and the activation of brain-targeting white blood cells. The aim was to determine if perinatal chronic hypoxia produces permanent injury to the brain, including a four-week recovery period. They found that mice exposed to perinatal chronic hypoxia lost myelin in the developing brain, which resulted in motor learning deficits that persisted for weeks after the end of hypoxic exposure. The long-term myelin loss was associated with increased inflammation in the brain, as well as an increased presence of CD4 T cells in the blood that were reactive to myelin. Therefore, perinatal chronic hypoxia induced an inflammatory response in the brain with concomitant demyelination, ultimately leading to long-term behavioral deficits.

"These findings are important since the neurological effects of low neonatal oxygen levels, if extended to humans, could have clinically actionable treatment options like oxygen supplementation," said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology. "The link between low oxygen or hypoxia and inflammation is becoming clear in a number of settings and the connection to inflammatory pathways may reveal additional anti-inflammatory treatment options for nervous system hypoxia."