Lipopolysaccharide Sensitizes Steroid-Induced Brain Injury in Neonatal Rat Pups

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.

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.

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.

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.