CONCISE COMMUNICATION Experimental Pneumococcal Meningitis in Mice: A Model of Intranasal Infection

Effective laboratory animal models of bacterial meningitis are needed to unravel the patho-physiology of this disease. Previous models have failed to simulate human meningitis by using a directly intracerebral route of infection. Hyaluronidase is a virulence factor of Streptococcus pneumoniae. In this study, a novel model of murine meningitis is described. Intranasal admin-istration of S. pneumoniae with hyaluronidase induced meningitis in 50 % of inoculated mice, as de®ned by a positive cerebrospinal ¯uid (CSF) culture and an in¯ammatory in®ltrate in the meninges. None of the mice inoculated without hyaluronidase developed meningitis. Hyal-uronidase was found to facilitate pneumococcal invasion of the bloodstream after colonization of the upper respiratory tract. Meningitis was characterized by pleocytosis of CSF and the induction of proin¯ammatory cytokines and CXC chemokines in brain tissue. These results indicate that this murine model mimics important features of human disease and allow for the use of this model for studying issues related to the pathophysiology and the treatment of pneumo-coccal meningitis. Bacterial meningitis due to Streptococcus pneumoniae is as-sociated with signi®cant mortality and morbidity, despite anti