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Published on: November 20, 2015
Lipopolysaccharide Sensitizes Steroid-Induced Brain Injury in Neonatal Rat Pups
Yu-Shan Chang1, Tzu-Mo Yang2, Yu-Ling Hsu3
1Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan.
Insights
Infection combined with corticosteroids like dexamethasone or hydrocortisone increases brain cell death and synaptic damage in developing rats. This suggests corticosteroids may worsen infection-induced brain injury in neonates.
Area of Science:
- Neonatal neuroscience
- Developmental neurobiology
- Pharmacology
Background:
- Infection is a known factor in bronchopulmonary dysplasia (BPD).
- Corticosteroids are frequently used for BPD prevention and treatment.
- Limited research exists on the combined effects of infection and corticosteroids on neonatal brain injury.
Purpose of the Study:
- To investigate the impact of infection combined with corticosteroid treatment on brain injury in neonatal rats.
- To examine the effects on cell death, synaptic integrity, and receptor expression.
Main Methods:
- Rat pups were exposed to lipopolysaccharide (LPS) on postnatal Day 1.
- Tapering doses of dexamethasone (Dex) or hydrocortisone (HC) were administered from Day 2 to 4.
- Evaluated body/brain weights, TUNEL-positive cells, synaptic protein levels (PSD95), and GR/MR mRNA expression.
Main Results:
- LPS combined with HC or Dex increased TUNEL-positive cells (oligodendrocyte precursors) in the hippocampus, cerebellum, and brain stem.
- Postsynaptic density protein 95 (PSD95) levels were reduced in these brain regions.
- GR mRNA decreased in multiple brain regions, and MR mRNA was reduced in the striatum.
Conclusions:
- Infection sensitizes the immature brain to corticosteroid-induced cell death and synaptic disruption.
- Altered glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) expression may mediate these effects.
- Findings highlight potential risks of corticosteroid use in infected neonates.
Background:
Infection is a pathogenetic factor for bronchopulmonary dysplasia (BPD), and corticosteroids are often used for its prevention or treatment. However, few studies have examined their combined effects on brain injury in the context of infection.
Methods:
Rat pups received lipopolysaccharide (LPS) on postnatal Day 1 (P1), followed by tapering doses of dexamethasone (Dex) or hydrocortisone (HC) from P2 to P4. We measured body and brain weights, TUNEL-positive cell counts, synaptic protein levels, and mRNA expression of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) in six brain regions at P5.
Results:
The LPS-HC and LPS-Dex groups showed more TUNEL-positive cells in the hippocampus, cerebellum, and brain stem compared to LPS-naïve controls. Oligodendrocyte precursor cells were the predominant TUNEL-positive cells in the hippocampus and brain stem. Additionally, the LPS-Dex or LPS-HC group showed significantly reduced levels of postsynaptic density protein 95 (PSD95), a postsynaptic protein, in these regions, while treatment with Dex or HC alone did not impact PSD95 expression. GR mRNA was significantly reduced in cortex, striatum, hippocampus, and cerebellum in LPS-HC group, with MR mRNA reduction limited primarily to the striatum.
Conclusions:
LPS sensitized the immature brain to Dex or HC-related cell death to possible apoptosis and augmented the LPS-induced disruption of synaptic integrity in certain brain regions, potentially via altered GR and MR expression that may modulate corticosteroid receptor signaling.
