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Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury
Published on: November 24, 2017
Longitudinal MR assessment of hypoxic ischemic injury in the immature rat brain
Yohan van de Looij1, Alexandra Chatagner, Petra S Hüppi
1Department of Pediatrics, Division of Child Development and Growth, University of Geneva, Geneva, Switzerland. yohan.vandelooij@epfl.ch
Insights
Neonatal hypoxic-ischemic injury in rat pups causes long-term brain damage, with males more affected. Early lactate increase predicts future cortical loss, offering potential for clinical prediction.
Area of Science:
- Neuroscience
- Developmental Biology
- Medical Imaging
Background:
- Extremely preterm infants often experience brain injuries with lasting effects.
- Three-day-old (P3) rat pups model early human cerebral development.
- Neonatal hypoxic-ischemic (HI) injury is a significant concern in preterm infants.
Purpose of the Study:
- To longitudinally assess structural and metabolic brain changes after moderate neonatal HI injury in P3 rat pups.
- To investigate the potential of early MRI and MRS findings for predicting long-term outcomes.
Main Methods:
- High-field (9.4 T) MRI and localized 1H magnetic resonance spectroscopy (MRS) were used.
- Rats were scanned longitudinally at postnatal days P3, P4, P11, and P25.
- Volumetric measurements and neurochemical profiling were performed.
Main Results:
- Cortical loss at P25 correlated with the size of damage at 6 hours post-HI; males were more severely affected.
- Metabolite concentrations acutely decreased with increased lactate 24 hours post-HI, followed by partial recovery.
- Elevated lactate at P4 correlated with P25 cortical loss, indicating early predictive value.
Conclusions:
- Moderate neonatal HI injury leads to long-term structural brain abnormalities in P3 rat pups.
- Early metabolic changes, particularly increased lactate, can predict long-term cortical damage.
- This model provides insights into predicting clinical outcomes in preterm infants post-HI injury.
Abstract:
Extremely preterm infants commonly show brain injury with long-term structural and functional consequences. Three-day-old (P3) rat pups share some similarities in terms of cerebral development with the very preterm infant (born at 24-28 weeks of gestation). The aim of this study was to assess longitudinally the cerebral structural and metabolic changes resulting from a moderate neonatal hypoxic ischemic injury in the P3 rat pup using high-field (9.4 T) MRI and localized (1) H magnetic resonance spectroscopy techniques. The rats were scanned longitudinally at P3, P4, P11, and P25. Volumetric measurements showed that the percentage of cortical loss in the long term correlated with size of damage 6 h after hypoxia-ischemia, male pups being more affected than female. The neurochemical profiles revealed an acute decrease of most of metabolite concentrations and an increase in lactate 24 h after hypoxia-ischemia, followed by a recovery phase leading to minor metabolic changes at P25 in spite of an abnormal brain development. Further, the increase of lactate concentration at P4 correlated with the cortical loss at P25, giving insight into the early prediction of long-term cerebral alterations following a moderate hypoxia-ischemia insult that could be of interest in clinical practice.
