The Role Of Inflammatory MiRNA146a And MiRNA132in Acute Meningitis Model

Part One:Establishment of the animal model for streptococcus pneumoniae meningitisObjective:To establish the rat model for SP meningitis.Materials and methods:We divided the animal model into4different groups; control (C), meningitis (M), meningitis with ceftriaxone (MA), and meningitis with both ceftriaxone and dexamethasone,(MSA). We injected streptococcus pneumoniae intra-cisternally in the rats to induce meningitis. After24hours, the rats were given ceftriaxone and dexamethasone. We measured the mortality rates and examined the CSF for the leucocyte count. Finally hematoxylin and eosin staining was performed on the cortical tissue.Results:We found an up-regulation in mortality rate and in leucocyte count, in the meningitis (M) group. The opposite was observed in the meningitis with ceftriaxone and dexamethasone,(MSA). Values in between (MSA) and (M) group, were recorded for the meningitis with ceftriaxone (MA) group as compared to the control,(C). Cortical tissue showed areas of necrosis under hematoxylin and eosin stain.Conclusion:We established the rat animal model for acute SP meningitis. Part Two:Do miRNA146a and miRNA132have a role in inflammation related to acute meningitis?Objective:The pathogenesis of bacterial meningitis due to streptococcus pneumoniae is still unclear. We want to investigate if miRNA146a and miRNA132take part in the inflammatory process in the acute model of SP meningitis.Materials and methods:SP induced rat meningitis models were taken and divided into4different groups; control (C), meningitis (M), meningitis with ceftriaxone (MA), and meningitis with both ceftriaxone and dexamethasone,(MSA). Western blot was used to detect TLR4, TNF α, IL1β, NFKB and real time PCR were used to detect the expression of miR132, miR146a respectively.Results:We found that the expression of TLR4, TNF α, IL1β, NFKB were all up-regulated in the acute stage of bacterial meningitis while down-regulated after being treated with antibiotics and steroids. While for the post transcription factors, the miRNAs146a and132, the opposite was observed, they were down-regulated in the meningitis group (M) when compared to the control (C) group. MiRNAs146a and132did not recover in the meningitis and ceftriaxone only group (MA) but in the (MSA) group in which steroids has been used as adjunct therapy (MSA) showed an increase in gene expression.Conclusion:miR132and146a may take part in the pathogenesis of SP bacterial meningitis. The modulation of anti-inflammatory process mediated by these miRNAs was likely to be related to the TLR4-NF-κB-TNF-α/IL-1βsignal transduction pathway.