title: Method for inducing experimental pneumococcal meningitis in outbred mice.
abstract: BACKGROUND
  Streptococcus pneumoniae is the leading cause of bacterial meningitis. Pneumococcal meningitis is associated with the highest mortality among bacterial meningitis and it may also lead to neurological sequelae despite the use of antibiotic therapy. Experimental animal models of pneumococcal meningitis are important to study the pathogenesis of meningitis, the host immune response induced after infection, and the efficacy of novel drugs and vaccines.
  
  
  RESULTS
  In the present work, we describe in detail a simple, reproducible and efficient method to induce pneumococcal meningitis in outbred mice by using the intracranial subarachnoidal route of infection. Bacteria were injected into the subarachnoid space through a soft point located 3.5 mm rostral from the bregma. The model was tested with several doses of pneumococci of three capsular serotypes (2, 3 and 4), and mice survival was recorded. Lethal doses killing 50 % of animals infected with type 2, 3 and 4 S. pneumoniae were 3.2 x 10, 2.9 x 10 and 1.9 x 10(2) colony forming units, respectively. Characterisation of the disease caused by the type 4 strain showed that in moribund mice systemic dissemination of pneumococci to blood and spleen occurred. Histological analysis of the brain of animals infected with type 4 S. pneumoniae proved the induction of meningitis closely resembling the disease in humans.
  
  
  CONCLUSIONS
  The proposed method for inducing pneumococcal meningitis in outbred mice is easy-to-perform, fast, cost-effective, and reproducible, irrespective of the serotype of pneumococci used.
authors.affiliation: Dipartimento di Biologia Molecolare, Laboratorio di Microbiologia Molecolare e Biotecnologia, Policlinico Le Scotte, Università di Siena, Viale Bracci, 53100 Siena, Italy. damianac@bu.edu <damianac@bu.edu>
authors.forename: Damiana
authors.initials: D
authors.lastname: Chiavolini
authors.forename: Sergio
authors.initials: S
authors.lastname: Tripodi
authors.forename: Riccardo
authors.initials: R
authors.lastname: Parigi
authors.forename: Marco R
authors.initials: MR
authors.lastname: Oggioni
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Blasi
authors.forename: Marcella
authors.initials: M
authors.lastname: Cintorino
authors.forename: Gianni
authors.initials: G
authors.lastname: Pozzi
authors.forename: Susanna
authors.initials: S
authors.lastname: Ricci
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000473:pathology; D001921:Brain / Q000382:microbiology; D015169:Colony Count, Microbial / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D007267:Injections / Q000379:methods; D008586:Meningitis, Pneumococcal / Q000401:mortality / Q000473:pathology*; D051379:Mice; D012703:Serotyping; D013154:Spleen / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000145:classification / Q000378:metabolism* / Q000472:pathogenicity; D013346:Subarachnoid Space / Q000382:microbiology; D016019:Survival Analysis