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Updated: Jul 6, 2026
Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Myelin expression is altered in the brains of neonatal rats reared in a fluctuating oxygen atmosphere
Kofi Sedowofia1, David Giles, Jean Wade
1Child Life and Health Section, Division of Reproductive and Developmental Sciences, University of Edinburgh, Edinburgh, UK.
Insights
Fluctuating blood oxygen levels in preterm infants can harm the developing brain
Area of Science:
- Neuroscience
- Neonatal Research
- Developmental Biology
Background:
- Preterm infants on oxygen therapy experience blood oxygen fluctuations.
- These fluctuations are linked to retinopathy of prematurity severity.
Purpose of the Study:
- Investigate if immature brains, particularly white matter, are susceptible to oxygen fluctuation-induced injury.
- Utilize a rat model to simulate preterm infant oxygen exposure.
Main Methods:
- Newborn rats exposed to computer-simulated oxygen fluctuations mirroring preterm infants.
- Measured active caspase-3, myelin basic protein (MBP), and glial fibrillary acidic protein (GFAP) expression.
- Compared exposed rats to room air controls over 14 and 21 days.
Main Results:
- Increased active caspase-3 and GFAP, decreased MBP in oxygen-exposed brains at day 14.
- GFAP and caspase-3 levels normalized by day 21, except in specific brain regions.
- MBP expression significantly increased in most brain regions by day 21.
Conclusions:
- Blood oxygen fluctuations may injure the developing brain's white matter and corpus striatum.
- This injury could contribute to neurological issues in extremely premature infants.
- Findings highlight the need for stable oxygenation in neonatal care.
Background:
Preterm infants receiving supplemental oxygen therapy experience frequent fluctuations in their blood oxygen levels, the magnitude of which has been associated with the incidence and severity of retinopathy of prematurity in such infants.
Objective:
Our objective was to investigate in a relevant animal model whether the immature brain with its poorly vascularised white matter might also be susceptible to injury when exposed to such fluctuations in blood oxygen.
Methods:
Newborn rats were reared in an atmosphere in which a computer reproduced the oxygen fluctuations derived from the transcutaneous oxygen levels of a 24-week preterm infant who had developed severe retinopathy. Following 14 days of exposure, we measured the expression of active caspase-3, myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) in the brains comparing with rat pups raised in room air.
Results:
Compared to room air controls, at day 14, the expression of active caspase-3 was increased by up to 162% (significant increase in 7 of 9 regions), MBP decreased by up to 70% (significant in the hypothalamus only) and GFAP increased by up to 103% (significant in 6 of 7 regions. On day 21, following 7 days of reparative recovery, GFAP levels in most areas of oxygen-exposed brains had returned to near control levels. There were no longer significant differences in caspase-3 levels apart from the cerebral cortex, cerebellum and striatum. In contrast, MBP expression was now much higher in most regions of the treated brains compared to controls.
Conclusion:
We conclude that fluctuations in blood oxygen, observed in preterm survivors, may constitute a source of injury to the white matter and corpus striatum of the developing brain and contribute to the neurological sequelae in extremely premature infants.
