Streptococcus pneumoniae is the most common pathogen causing non-epidemic
bacterial meningitis worldwide. The immune response and inflammatory processes contribute to the pathophysiology. Hence, the anti-inflammatory
dexamethasone is advocated as adjuvant treatment although its clinical efficacy remains a question at issue. In experimental models of
pneumococcal meningitis,
dexamethasone increased neuronal damage in the dentate gyrus. Here, we investigated expressional changes in the hippocampus and cortex at 72 h after
infection when
dexamethasone was given to infant rats with
pneumococcal meningitis. Nursing Wistar rats were intracisternally infected with Streptococcus pneumoniae to induce experimental
meningitis or were
sham-infected with
pyrogen-free saline. Besides
antibiotics, animals were either treated with
dexamethasone or saline. Expressional changes were assessed by the use of GeneChip® Rat Exon 1.0 ST Arrays and quantitative real-time PCR.
Protein levels of
brain-derived neurotrophic factor,
cytokines and
chemokines were evaluated in immunoassays using Luminex xMAP® technology. In infected animals, 213 and 264 genes were significantly regulated by
dexamethasone in the hippocampus and cortex respectively. Separately for the cortex and the hippocampus, Gene Ontology analysis identified clusters of biological processes which were assigned to the predefined categories "
inflammation", "growth", "apoptosis" and others.
Dexamethasone affected the expression of genes and
protein levels of
chemokines reflecting diminished activation of microglia.
Dexamethasone-induced changes of genes related to apoptosis suggest the downregulation of the Akt-survival pathway and the induction of
caspase-independent apoptosis. Signalling of pro-neurogenic pathways such as
transforming growth factor pathway was reduced by
dexamethasone resulting in a lack of pro-survival triggers. The anti-inflammatory properties of
dexamethasone were observed on gene and
protein level in
experimental pneumococcal meningitis. Further
dexamethasone-induced expressional changes reflect an increase of pro-apoptotic signals and a decrease of pro-neurogenic processes. The findings may help to identify potential mechanisms leading to apoptosis by
dexamethasone in
experimental pneumococcal meningitis.