title: Inhibition of matrix metalloproteinases attenuates brain damage in experimental meningococcal meningitis.
abstract: BACKGROUND
  Approximately 7% of survivors from meningococcal meningitis (MM) suffer from neurological sequelae due to brain damage in the course of meningitis. The present study focuses on the role of matrix metalloproteinases (MMPs) in a novel mouse model of MM-induced brain damage.
  
  
  METHODS
  The model is based on intracisternal infection of BALB/c mice with a serogroup C Neisseria meningitidis strain. Mice were infected with meningococci and randomised for treatment with the MMP inhibitor batimastat (BB-94) or vehicle. Animal survival, brain injury and host-response biomarkers were assessed 48 h after meningococcal challenge.
  
  
  RESULTS
  Mice that received BB-94 presented significantly diminished MMP-9 levels (p < 0.01), intracerebral bleeding (p < 0.01), and blood-brain barrier (BBB) breakdown (p < 0.05) in comparison with untreated animals. In mice suffering from MM, the amount of MMP-9 measured by zymography significantly correlated with both intracerebral haemorrhage (p < 0.01) and BBB disruption (p < 0.05).
  
  
  CONCLUSIONS
  MMPs significantly contribute to brain damage associated with experimental MM. Inhibition of MMPs reduces intracranial complications in mice suffering from MM, representing a potential adjuvant strategy in MM post-infection sequelae.
authors.forename: Susanna
authors.initials: S
authors.lastname: Ricci
authors.forename: Denis
authors.initials: D
authors.lastname: Grandgirard
authors.forename: Michael
authors.initials: M
authors.lastname: Wenzel
authors.forename: Tiziana
authors.initials: T
authors.lastname: Braccini
authors.forename: Paola
authors.initials: P
authors.lastname: Salvatore
authors.forename: Marco R
authors.initials: MR
authors.lastname: Oggioni
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Leib
authors.forename: Uwe
authors.initials: U
authors.lastname: Koedel
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000473:pathology*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D053208:Kaplan-Meier Estimate; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008585:Meningitis, Meningococcal / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018925:Chemokines; D016207:Cytokines; D061965:Matrix Metalloproteinase Inhibitors; D013876:Thiophenes; D010649:Phenylalanine; C080985:batimastat; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9