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: Susanna Ricci, Denis Grandgirard, Michael Wenzel, Tiziana Braccini, Paola Salvatore, Marco R Oggioni, Stephen L Leib, Uwe Koedel
• Journal: BMC infectious diseases (BMC Infect Dis) Vol. 14 Pg. 726 (Dec 31 2014) ISSN: 1471-2334 [Electronic] England
• PMID: 25551808 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokines
• Cytokines
• Matrix Metalloproteinase Inhibitors
• Thiophenes
• Phenylalanine
• batimastat
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Animals
• Apoptosis (drug effects)
• Blood-Brain Barrier (drug effects, pathology)
• Cerebellum (drug effects, metabolism)
• Cerebral Hemorrhage (complications, drug therapy, enzymology, pathology)
• Chemokines (metabolism)
• Cytokines (metabolism)
• Dentate Gyrus (drug effects, pathology)
• Disease Models, Animal
• Female
• Kaplan-Meier Estimate
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Matrix Metalloproteinase Inhibitors (pharmacology, therapeutic use)
• Meningitis, Meningococcal (complications, drug therapy, enzymology, pathology)
• Mice
• Phenylalanine (analogs & derivatives, pharmacology, therapeutic use)
• Thiophenes (pharmacology, therapeutic use)