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Updated: May 4, 2026
Early Pathological and Magnetic Resonance Detection of Cerebral Injury Using a Rat Model of Neonatal Hypoxic Ischemic Encephalopathy
Published on: October 28, 2022
Brain development after neonatal intermittent hyperoxia-hypoxia in the rat studied by longitudinal MRI and
Tora Sund Morken1, Axel Karl Gottfrid Nyman2, Ioanna Sandvig2
1Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Insights
Neonatal intermittent hyperoxia-hypoxia (IHH) caused temporary brain white matter changes and increased vascular density in rat pups. These effects were more severe in lower-birth-weight animals, suggesting potential long-term impacts on brain development.
Area of Science:
- Neuroscience
- Neonatal Physiology
- Developmental Biology
Background:
- Neonatal intermittent hyperoxia-hypoxia (IHH) is linked to retinopathy of prematurity.
- The impact of IHH on neonatal brain grey and white matter is not well understood.
Purpose of the Study:
- To investigate the pathological changes in neonatal rat brain grey and white matter following IHH exposure.
- To assess the reversibility of these changes and potential long-term neurodevelopmental effects.
Main Methods:
- Rat pups were exposed to IHH (alternating hyperoxia and hypoxia) from birth to P14.
- Longitudinal MRI (Diffusion Tensor Imaging, T2-mapping) was performed at P14 and P28.
- Histopathological examination and neurodevelopmental assessments (Rotarod) were conducted.
Main Results:
- IHH induced reversible white matter diffusivity changes and increased cortical vessel density at P14.
- Albumin leakage indicated blood-brain barrier alterations by P28.
- IHH-exposed rats showed improved Rotarod performance, with lower body weight correlating with more severe MRI changes.
Conclusions:
- IHH causes subtle, reversible brain white matter and grey matter changes.
- Blood-brain barrier permeability alterations suggest potential long-term neurological consequences.
- Growth restriction may exacerbate IHH-induced brain alterations, warranting further investigation.
Background:
Neonatal intermittent hyperoxia-hypoxia (IHH) is involved in the pathogenesis of retinopathy of prematurity. Whether similar oxygen fluctuations will create pathological changes in the grey and white matter of the brain is unknown.
Methods:
From birth until postnatal day 14 (P14), two litters (total n = 22) were reared in IHH: hyperoxia (50% O2) interrupted by three consecutive two-minute episodes of hypoxia (12% O2) every sixth hour. Controls (n = 8) were reared in room-air (20.9% O2). Longitudinal MRI (Diffusion Tensor Imaging and T2-mapping) was performed on P14 and P28 and retinal and brain tissue were examined for histopathological changes. Long-term neurodevelopment was assessed on P20 and P27.
Results:
Mean, radial and axial diffusivity were higher in white matter of IHH versus controls at P14 (p < 0.04), while fractional anisotropy (FA) was lower in the hippocampal fimbria and tended to be lower in corpus callosum (p = 0.08) and external capsule (p = 0.05). White matter diffusivity in IHH was similar to controls at P28. Higher cortical vessel density (p = 0.005) was observed at P14. Cortical and thalamic T2-relaxation time and mean diffusivity were higher in the IHH group at P14 (p ≤ 0.03), and albumin leakage was present at P28. Rats in the IHH group ran for a longer time on a Rotarod than the control group (p ≤ 0.005). Pups with lower bodyweight had more severe MRI alterations and albumin leakage.
Conclusion:
IHH led to subtle reversible changes in brain white matter diffusivity, grey matter water content and vascular density. However, alterations in blood-brain barrier permeability may point to long-term effects. The changes seen after IHH exposure were more severe in animals with lower bodyweight and future studies should aim at exploring possible interactions between IHH and growth restriction.
