Abstract
Inhaled nitric oxide (iNO) enhances ventilation in very preterm infants, but the effects on the brain remain uncertain. We evaluated the impact of iNO on brain growth and cerebral injury in a premature baboon model. Baboons were delivered at 125 d of gestation (term 185 d of gestation) and ventilated for 14 d with either positive pressure ventilation (PPV) (n = 7) or PPV + iNO (n = 8). Brains were assessed histologically for parameters of development and injury. Compared with gestational controls (n = 7), brain and body weights were reduced but brain-to-body weight ratios were increased in all prematurely delivered (PD) animals; the surface folding index (SFI), was reduced in PPV but not PPV + iNO animals. Compared with controls, the brain damage index was increased (p < 0.05) in both cohorts of PD animals. There was no difference between ventilatory regimens, however, in 25% of animals with iNO therapy, there were organized hematomas in the subarachnoid space. Overall, iNO did not alter the extent of brain damage but did result in the presence of hematomas. These results do not confirm any protective or major injurious effect of nitric oxide therapy on the developing brain.
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Abbreviations
- GFAP:
-
glial fibrillary acidic protein
- H&E:
-
hematoxylin and eosin
- iNO:
-
inhaled nitric oxide
- IVH:
-
intraventricular hemorrhage
- MBP:
-
myelin basic protein
- PD:
-
premature delivery
- PPV:
-
positive pressure ventilation
- SFI:
-
surface folding index
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Acknowledgements
The authors are most grateful to Ms. Winter and Dr. Coalson at the SFBR for provision of baboon tissue and to Drs. Folkerth and Kinney, Department of Pathology, Children's Hospital, Boston, MA, for neuropathologic advice. Dr. Dalitz provided invaluable assistance with some of the immunohistochemistry.
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Supported by NIH grant R01 HL074942 and in part by grants from the National Institutes of Health (NHLBI grant HL-52636 and U01-HL063399) and the National Center for Research Resources to the Southwest National Primate Research Center (P51 RR013986).
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Rees, S., Camm, E., Loeliger, M. et al. Inhaled Nitric Oxide: Effects on Cerebral Growth and Injury in a Baboon Model of Premature Delivery. Pediatr Res 61, 552–558 (2007). https://doi.org/10.1203/pdr.0b013e318045be20
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DOI: https://doi.org/10.1203/pdr.0b013e318045be20
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