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Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Impact of bronchopulmonary dysplasia on brain and retina
Annie Wing Hoi Poon1, Emilie Xiao Hang Ma1, Arul Vadivel2
1Division of Newborn Medicine, Department of Pediatrics, McGill University, Montreal, Quebec H4A 3J1, Canada.
Insights
High oxygen exposure in premature infants causes lung damage similar to bronchopulmonary dysplasia (BPD) and also harms brain and retinal development. Severe lung injury correlated with worse brain and eye outcomes in this animal model.
Area of Science:
- Neonatal physiology
- Developmental biology
- Ophthalmology
Background:
- Premature newborns often develop bronchopulmonary dysplasia (BPD) due to mechanical ventilation and hyperoxia.
- BPD survivors experience long-term lung, brain, and retinal injuries, but the cause is unclear.
Purpose of the Study:
- To investigate if hyperoxia, a cause of BPD lung changes, also induces brain and retinal injuries.
- To determine if lung, brain, and retinal injuries are linked in a neonatal hyperoxia model.
Main Methods:
- Sprague Dawley rat pups exposed to 95% O2 (hyperoxia) or room air from postnatal day 4-14.
- Lung, brain, and retinal tissues analyzed at postnatal day 28 using H&E and Toluidine Blue staining.
- Histological measurements of lung structures, brain surface area, and retinal layer thickness.
Main Results:
- Hyperoxia significantly increased lung injury (mean linear intercept).
- Hyperoxia exposure decreased whole-brain surface area and retinal layer thickness.
- Severe lung injury correlated negatively with brain (r=-0.49) and retinal (r=-0.70) structures.
Conclusions:
- Neonatal hyperoxia exposure impairs lung, brain, and retinal development.
- The severity of lung injury is associated with the severity of brain and retinal damage.
- This animal model can be used to study hyperoxia-induced injuries across multiple organs.
Abstract:
Many premature newborns develop bronchopulmonary dysplasia (BPD), a chronic lung disease resulting from prolonged mechanical ventilation and hyperoxia. BPD survivors typically suffer long-term injuries not only to the lungs, but also to the brain and retina. However, currently it is not clear whether the brain and retinal injuries in these newborns are related only to their prematurity, or also to BPD. We investigated whether the hyperoxia known to cause histologic changes in the lungs similar to BPD in an animal model also causes brain and retinal injuries. Sprague Dawley rat pups were exposed to hyperoxia (95% O2, 'BPD' group) or room air (21% O2, 'control' group) from postnatal day 4-14 (P4-14); the rat pups were housed in room air between P14 and P28. At P28, they were sacrificed, and their lungs, brain, and eyes were extracted. Hematoxylin and eosin staining was performed on lung and brain sections; retinas were stained with Toluidine Blue. Hyperoxia exposure resulted in an increased mean linear intercept in the lungs (P<0.0001). This increase was associated with a decrease in some brain structures [especially the whole-brain surface (P=0.02)], as well as a decrease in the thickness of the retinal layers [especially the total retina (P=0.0008)], compared to the room air control group. In addition, a significant negative relationship was observed between the lung structures and the brain (r=-0.49,P=0.02) and retina (r=-0.70,P=0.0008) structures. In conclusion, hyperoxia exposure impaired lung, brain, and retina structures. More severe lung injuries correlated with more severe brain and retinal injuries. This result suggests that the same animal model of chronic neonatal hyperoxia can be used to simultaneously study lung, brain and retinal injuries related to hyperoxia.
