is the most common pathogen causing non-epidemic bacterial meningitis worldwide. meningitis. Nursing Wistar rats were intracisternally infected with 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 element cytokines and chemokines were evaluated in immunoassays using Luminex xMAP? technology. In contaminated pets 213 and 264 genes had been controlled by dexamethasone in the hippocampus and cortex respectively significantly. Individually for the cortex as well as the hippocampus Gene Ontology evaluation discovered clusters of natural procedures which were designated towards the predefined types “irritation” “development” “apoptosis” among others. Dexamethasone affected the appearance of proteins and genes degrees of chemokines reflecting reduced activation of microglia. Dexamethasone-induced adjustments of genes linked to apoptosis recommend the downregulation from the Akt-survival pathway as well as the induction of caspase-independent apoptosis. Signalling of pro-neurogenic pathways such as for example transforming growth aspect pathway was decreased by dexamethasone producing a insufficient pro-survival triggers. The EKB-569 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. Intro Treatment of bacterial meningitis (BM) with sulfonamids was successfully launched in the 1930’s and the introduction of third generation cephalosporins further reduced EKB-569 the mortality rates . Since then improvements in treatment success are scarce and the mortality rate of BM still reaches 34% and up to 50% EKB-569 of the survivors suffer from neurologic sequelae  . Among the different pathogens causing community-acquired meningitis in industrialized countries accounts for the majority of cases and shows the highest mortality rate    . Studies investigating the pathophysiology of BM exposed that not only the pathogen itself exerts harmful Gpc4 effects but also the pronounced immune response of the sponsor  . Neurological complications such as improved intracranial pressure cerebral ischemia mind edema development or hydrocephalus can result in a fatal final result . Histopathological assessments in experimental versions aswell as autopsy situations showed three types of damage in the central anxious program: apoptosis takes place in the hippocampal dentate gyrus necrosis is situated in the cerebral cortex and lack of type 1 neurons in the spiral ganglion. These types of neuronal harm trigger neurological sequelae such as for example learning deficits seizure disorders and hearing impairments respectively   . To be able to decrease the inflammatory response the glucocorticoid (GC) dexamethasone (dex) is normally advocated in sufferers with BM furthermore to antibiotic treatment. Execution of adjuvant therapy with dex (10 mg IV provided every 6 hours for 4 times began before or using the initial dosage of parenteral antibiotics) decreased mortality price as well as the percentage of sufferers with unfavorable final results in holland . Worldwide however a meta-analysis including 2029 individual patient data concluded that the benefit of dex in BM remains unproven . In experimental models both detrimental and beneficial effects of adjunctive dex have been observed. Dex increased the number of apoptotic cells in the hippocampal dentate gyrus of infant rats with pneumococcal meningitis (PM) and of rabbits with or PM    and led to decreased learning overall performance . In different animals models however Dex was shown to have otoprotective effects in experimental pneumococcal meningitis EKB-569 in gerbils   or rabbits  and to improve neurobehavioral overall performance in adult rats with group B streptococcal meningitis . A study assessing the transcriptome in experimental PM recognized Gene Ontology (GO) terms related to “neuron generation” and “nervous tissue development” to be overrepresented when comparing the hippocampus of contaminated vs..