Abstract
Streptococcus pneumoniae meningitis is an infection of the central nervous system associated with high mortality rates and serious neurologic sequelae in children. The principal reason for the severity of S. pneumoniae meningitis is widespread ignorance of the pathogenesis of the disease. This study aimed at exploring whether cysteinyl leukotriene receptor (CysLTR) participates in the inflammatory response and elucidates the pathologic process of S. pneumoniae meningitis. Bacterial meningitis disease models were constructed by intracisternal inoculation of rats with serotype III Streptococcus pneumoniae while control models were inoculated with the same volume of normal saline. Rats were sacrificed at different time points (1 d, 2 d, and 5 d) following the administration of Streptococcus pneumoniae. Results from the body-weight, Loeffler neurologic deficit score, and cerebrospinal fluid culture confirmed that a successful pneumococcal meningitis rat model was established. Pathologic changes in brain tissues mainly consisted of inflammation in the meninges and subarachnoid space and significant neuronal injury in the cerebral cortex and hippocampus (P < 0.05). Immunohistochemical analysis revealed that microglial activation and astrocyte proliferation were associated with the development of bacterial meningitis. The expression levels of CysLTR and inflammatory factor tumor necrosis factor-α (TNF-α) were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis. The results of this study indicate that CysLTR expression was markedly elevated in the 5 d infection group (P < 0.05), which was consistent with time-dependent release of TNF-α. The findings of this study indicate that CysLTR participates in the pneumococcal meningitis infection process by mediating neuronal injury and glial cell proliferation. Cysteinyl leukotriene receptors could, therefore, be novel targets to mitigate the progression of pneumococcal meningitis.