Mild intermittent hypoxemia in neonatal mice causes permanent neurofunctional deficit and white matter hypomyelination

Courtney Juliano, Sergey Sosunov, Zoya Niatsetskaya, Joseph A. Isler, Irina Utkina-Sosunova, Isaac Jang, Veniamin Ratner, Vadim Ten

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Very Low Birth Weight (VLBW) premature infants experience numerous, often self-limited non-bradycardic episodes of intermittent hypoxemia (IH). We hypothesized that these episodes of IH affect postnatal white matter (WM) development causing hypomyelination and neurological handicap in the absence of cellular degeneration. Based on clinical data from ten VLBW neonates; a severity, daily duration and frequency of non-bradycardic IH episodes were reproduced in neonatal mice. Changes in heart rate and cerebral blood flow during IH were recorded. A short-term and long-term neurofunctional performance, cerebral content of myelin basic protein (MBP), 2'3' cyclic-nucleotide 3-phosphodiesterase (CNPase), electron microscopy of axonal myelination and the extent of cellular degeneration were examined.Neonatal mice exposed to IH exhibited no signs of cellular degeneration, yet demonstrated significantly poorer olfactory discrimination, wire holding, beam and bridge crossing, and walking-initiation tests performance compared to controls. In adulthood, IH-mice demonstrated no alteration in navigational memory. However, sensorimotor performance on rota-rod, wire-holding and beam tests was significantly worse compared to naive littermates. Both short- and long-term neurofunctional deficits were coupled with decreased MBP, CNPase content and poorer axonal myelination compared to controls.In neonatal mice mild, non-ischemic IH stress, mimicking that in VLBW preterm infants, replicates a key phenotype of non-cystic WM injury: permanent hypomyelination and sensorimotor deficits. Because this phenotype has developed in the absence of cellular degeneration, our data suggest that cellular mechanisms of WM injury induced by mild IH differ from that of cystic periventricular leukomalacia where the loss of myelin-producing cells and axons is the major mechanism of injury.

Original languageEnglish
Pages (from-to)33-42
Number of pages10
JournalExperimental Neurology
StatePublished - 1 Feb 2015
Externally publishedYes


  • Hypomyelination
  • Intermittent hypoxemia
  • Model
  • Sensori-motor deficit
  • White matter injury


Dive into the research topics of 'Mild intermittent hypoxemia in neonatal mice causes permanent neurofunctional deficit and white matter hypomyelination'. Together they form a unique fingerprint.

Cite this