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Updated: Mar 12, 2026
The Hypoxic Ischemic Encephalopathy Model of Perinatal Ischemia
Published on: November 19, 2008
Neonatal Dexamethasone Treatment Exacerbates Hypoxia/Ischemia-Induced White Matter Injury
Chia -Yu Yeh1, Che-Ming Yeh2, Ting-Hsuan Yu2
1Department of Pharmacology, College of Medicine, National Cheng Kung University, No. 1, University Rd, Tainan, 701, Taiwan.
Insights
Neonatal dexamethasone (DEX) treatment worsens white matter injury from hypoxia/ischemia in developing rat brains. However, the antibiotic ceftriaxone shows promise in mitigating this damage and improving motor function.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Dexamethasone (DEX) is used to treat preterm infants with chronic lung disease.
- Concerns exist regarding DEX's adverse effects on fetal brain development.
- Previous studies linked neonatal DEX to increased vulnerability to gray matter injury after hypoxia/ischemia (HI).
Purpose of the Study:
- To investigate the impact of neonatal DEX treatment on hypoxia/ischemia (HI)-induced subcortical white matter (WM) injury in the developing rat brain.
- To assess if DEX exacerbates WM injury, oligodendroglial cell development, and motor deficits following HI.
- To evaluate the potential of ceftriaxone to ameliorate DEX-induced exacerbation of HI brain injury.
Main Methods:
- A hypoxia/ischemia (HI) model was used in rat pups.
- Neonatal rats received a tapering course of dexamethasone (DEX) on postnatal days 1-3.
- Oligodendroglial lineage cells, apoptosis, astrocyte activation, myelin thickness, axon caliber, and motor function were assessed.
- The effect of ceftriaxone administration on HI-induced WM injury was examined.
Main Results:
- Neonatal DEX treatment significantly reduced oligodendroglial lineage cells and exacerbated HI-induced white matter (WM) injury.
- DEX enhanced HI-induced oligodendroglial apoptosis and astrocyte activation in the developing WM.
- HI-induced deficits in myelin thickness, axon caliber, and function were worsened by neonatal DEX.
- DEX treatment aggravated HI-induced motor deficits.
- Ceftriaxone administration reduced HI-induced WM injury in DEX-treated rats.
Conclusions:
- Neonatal dexamethasone treatment increases vulnerability of the developing brain to hypoxia/ischemia-induced white matter injury.
- DEX negatively impacts oligodendroglial development and function, contributing to exacerbated injury.
- Ceftriaxone shows potential as a therapeutic agent to counteract DEX-induced neurotoxicity and HI injury.
Abstract:
Dexamethasone, a synthetic glucocorticoid, has been widely used to prevent or ameliorate morbidity of chronic lung disease in preterm infants with respiratory distress syndrome. Despite its beneficial effect on neonatal lung function, growing concern has arisen about adverse effects of this clinical practice on fetal brain development. We demonstrated previously that neonatal dexamethasone (DEX) treatment may render the newborn brain to be more vulnerable to hypoxia/ischemia (HI)-induced gray matter injury. Here, we examined whether neonatal DEX treatment may also affect the extent of HI-induced subcortical white matter (WM) injury in the developing rat brain. Using a HI model of premature brain injury, we demonstrated that a 3-day tapering course (0.5, 0.3, and 0.1 mg/kg) of DEX treatment in rat pups on postnatal days 1-3 (P1-3) significantly reduced the number of all stages of the oligodendroglial lineage cells on P7 and exacerbated HI-induced WM injury. Neonatal DEX treatment also enhanced HI-induced oligodendroglial apoptosis and astrocyte activation in the developing WM on P14. Likewise, HI-induced reductions in myelin thickness, axon caliber, and function during WM development were exacerbated by neonatal DEX treatment. Furthermore, neonatal DEX treatment further aggravated HI-induced motor deficits as assessed in the rotarod test. We also found that the administration of β-lactam antibiotic ceftriaxone increased glutamate transporter-1 protein expression and significantly reduced HI-induced WM injury in neonatal DEX-treated rats. These results suggest that neonatal DEX treatment may lead the developing brain to be more vulnerable to subsequent HI-induced WM injury, which can be ameliorated by ceftriaxone administration.
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