Inhibition of matrix metalloproteinases attenuates brain damage in experimental meningococcal meningitis

BMC Infectious Diseases

Uwe Koedel¹  Stephen L Leib¹  Marco R Oggioni¹  Paola Salvatore²  Tiziana Braccini³  Michael Wenzel⁴  Denis Grandgirard¹  Susanna Ricci¹ 

[1] The ESCMID Study Group for Infectious Diseases of the Brain (ESGIB), Basel, Switzerland;Department of Molecular Medicine and Medical Biotechnology, Federico II University Medical School, Naples, Italy;Department of Medical Biotechnologies, Laboratory of Molecular Microbiology and Biotechnology (LA.M.M.B.), Ospedale Santa Maria alle Scotte (V lotto, piano 1), University of Siena, Viale Bracci, Siena, 53100, Italy;Present address: Columbia University, Biological Sciences, 901 NWC Building, 550 West 120th Street, New York 10027, NY, USA

关键词: Metalloproteinase inhibitors;    Matrix metalloproteinases;    Brain damage;    Mouse model;    Meningococcal meningitis;    Neisseria meningitidis;   

Others  :  1090013
DOI  :  10.1186/s12879-014-0726-6

 received in 2014-10-07, accepted in 2014-12-18,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Ricci et al.; licensee BioMed Central.

【 图 表 】

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