Gestational intermittent hypoxia increases susceptibility to neuroinflammation and alters respiratory motor control in neonatal rats

•Sleep-disordered breathing (SDB) during pregnancy is a growing clinical problem.•Fetal exposure to intermittent hypoxia has deleterious effects.•Gestational intermittent hypoxia in rats altered CNS immune response to LPS challenge.•Gestational intermittent hypoxia in rats altered respiratory motor...

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Bibliographic Details
Published in:Respiratory physiology & neurobiology 2018-10, Vol.256, p.128-142
Main Authors: Johnson, Stephen M., Randhawa, Karanbir S., Epstein, Jenna J., Gustafson, Ellen, Hocker, Austin D., Huxtable, Adrianne G., Baker, Tracy L., Watters, Jyoti J.
Format: Article
Language:English
Subjects:
Critical period
Inflammation
Intermittent hypoxia
Neonates
Pregnancy
Respiratory rhythm generation
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Summary:•Sleep-disordered breathing (SDB) during pregnancy is a growing clinical problem.•Fetal exposure to intermittent hypoxia has deleterious effects.•Gestational intermittent hypoxia in rats altered CNS immune response to LPS challenge.•Gestational intermittent hypoxia in rats altered respiratory motor responses to LPS.•Long-term consequences of SDB require further investigation. Sleep disordered breathing (SDB) and obstructive sleep apnea (OSA) during pregnancy are growing health concerns because these conditions are associated with adverse outcomes for newborn infants. SDB/OSA during pregnancy exposes the mother and the fetus to intermittent hypoxia. Direct exposure of adults and neonates to IH causes neuroinflammation and neuronal apoptosis, and exposure to IH during gestation (GIH) causes long-term deficits in offspring respiratory function. However, the role of neuroinflammation in CNS respiratory control centers of GIH offspring has not been investigated. Thus, the goal of this hybrid review/research article is to comprehensively review the available literature both in humans and experimental rodent models of SDB in order to highlight key gaps in knowledge. To begin to address some of these gaps, we also include data demonstrating the consequences of GIH on respiratory rhythm generation and neuroinflammation in CNS respiratory control regions. Pregnant rats were exposed to daily intermittent hypoxia during gestation (G10-G21). Neuroinflammation in brainstem and cervical spinal cord was evaluated in P0-P3 pups that were injected with saline or lipopolysaccharide (LPS; 0.1mg/kg, 3h). In CNS respiratory control centers, we found that GIH attenuated the normal CNS immune response to LPS challenge in a gene-, sex-, and CNS region-specific manner. GIH also altered normal respiratory motor responses to LPS in newborn offspring brainstem-spinal cord preparations. These data underscore the need for further study of the long-term consequences of maternal SDB on the relationship between inflammation and the respiratory control system, in both neonatal and adult offspring.
ISSN:1569-9048
1878-1519
DOI:10.1016/j.resp.2017.11.007