A neonatal mouse model of intermittent hypoxia associated with features of apnea in premature infants

Abstract

A neonatal mouse model of intermittent hypoxia (IH) simulating the recurring hypoxia/reoxygenation episodes of apnea of prematurity (AOP) was developed. C57BL/6 P2 pups were culled for exposure to either intermittent hypoxia or intermittent air as control. The IH paradigms consisted of alternation cycles of 20.9% O2 and either 8.0% or 5.7% O2 every 120 or 140 seconds for 6 hours a day during daylight hours from day 2 to day 10 postnatally, i.e., roughly equivalent to human brain development in the perinatal period. IH exposures elicited modest to severe decrease in oxygen saturation along with bradycardia in neonatal mice, which were severity-dependent. Hypomyelination in both central and peripheral nervous systems was observed despite the absence of visible growth retardation. The neonatal mouse model of IH in this study partially fulfills the current diagnostic criteria with features of AOP, and provides opportunities to reproduce in rodents some of the pathophysiological changes associated with this disorder, such as alterations in myelination.

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

“…There are several reports exploring the role of experimental intermittent hypoxemia in neurologic morbidity associated with adult sleep apnea and apnea of prematurity (Cai et al, 2011(Cai et al, , 2012Douglas et al, 2010;Oorschot et al, 2013;Xu et al, 2004). Similar to our results, studies on neonatal animals demonstrated poorer WM myelination in mice and rats exposed to IH compared to their naïve controls.…”

Metallothionein deletion exacerbates intermittent hypoxia-induced renal injury in mice

“…The murine model of IH exposures during sleep was used in this study as previous reports (Cai et al, 2011(Cai et al, , 2012b. Briefly, adult mice were exposed to an IH profile designed to produce similar nadir hemoglobin oxygen saturations (50-60%) and apnea/ hypopnea index (21-50 times/h) as observed in moderate to severe OSA patients.…”

Cerebral Autoregulation, Brain Injury, and the Transitioning Premature Infant

“…This vulnerability can be intrinsic, caused by excessive glutathione depletion from oxidative stress or extrinsic, caused by glutamate receptor-mediated toxicity, the result of glutamate release by adjacent dying cells (14). Either mechanism sets up a cascade of events, leading to loss of pre-OLs and damage to surrounding white matter (15–17). …”