Abstract
Background
Preterm infants are frequently exposed to intermittent hypoxia (IH) associated with apnea and periodic breathing that may result in inflammation and brain injury that later manifests as cognitive and executive function deficits. We used a rodent model to determine whether early postnatal exposure to IH would result in inflammation and brain injury.
Methods
Rat pups were exposed to IH from P2 to P12. Control animals were exposed to room air. Cytokines were analyzed in plasma and brain tissue at P13 and P18. At P20–P22, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) were performed.
Results
Pups exposed to IH had increased plasma Gro/CXCL1 and cerebellar IFN-γ and IL-1β at P13, and brainstem enolase at P18. DTI showed a decrease in FA and AD in the corpus callosum (CC) and cingulate gyrus, and an increase in RD in the CC. MRS revealed decreases in NAA/Cho, Cr, Tau/Cr, and Gly/Cr; increases in TCho and GPC in the brainstem; and decreases in NAA/Cho in the hippocampus.
Conclusions
We conclude that early postnatal exposure to IH, similar in magnitude to that experienced in human preterm infants, is associated with evidence for proinflammatory changes, decreases in white matter integrity, and metabolic changes consistent with hypoxia.
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Acknowledgements
STATEMENT OF FINANCIAL SUPPORT
We thank Luxi Xia for helping us with the animals. The data have been partially presented at the Experimental Biology Annual meeting in April 2016, the PAS meeting in May 2016, and the MRS results at the SPIE.Medical Imaging meeting in February, 2017 (Darnall RA et al, Proc SPIE Int Soc Opt Eng 10137:101371Y, 2017).
These studies were supported by grants from the NIH, NIH PO1 HD36379; The American SIDS Institute; and The Hearst Foundation, Department of Pediatrics, Dartmouth Geisel School of Medicine, NIH NCMRR/NINDS 2R24HD050846-06 (NCMRR-DC Core Molecular and Functional Outcome Measures in Rehabilitation Medicine). 9.4T Magnet for MRI studies was funded by NIH 1S10RR025048-01.
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Darnall, R., Chen, X., Nemani, K. et al. Early postnatal exposure to intermittent hypoxia in rodents is proinflammatory, impairs white matter integrity, and alters brain metabolism. Pediatr Res 82, 164–172 (2017). https://doi.org/10.1038/pr.2017.102
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DOI: https://doi.org/10.1038/pr.2017.102
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