Elsevier

Neuroscience Letters

Volume 338, Issue 3, 6 March 2003, Pages 201-204
Neuroscience Letters

Matrix metalloproteinase-9 deficiency impairs host defense mechanisms against Streptococcus pneumoniae in a mouse model of bacterial meningitis

https://doi.org/10.1016/S0304-3940(02)01406-4Get rights and content

Abstract

Matrix metalloproteinase-9 (MMP-9) appears to contribute to blood–brain barrier damage and neuronal injury in bacterial meningitis. To further explore the function of MMP-9 in meningeal inflammation, we injected 104 colony forming units (CFU) of a Streptoccocus pneumoniae type 3 strain into the right forebrain of MMP-9 deficient mice (MMP-9−/−, n=16) and wild-type controls (129×B6, n=15). The clinical course of the disease, leukocyte recruitment into the subarachnoid space and bacterial titers in the brain did not differ. Yet, clearance of the bacteria from blood (log CFU/ml 4.7 [3.8/5.4] vs. 3.6 [3.0/4.0]; P=0.005) and spleen homogenates (log CFU/ml 5.3 [4.8/5.5] vs. 4.0 [2.8/4.7]; P=0.01) was reduced in MMP-9 deficient mice. A reduced systemic bacterial clearance of MMP-9−/− mice was confirmed in experimental S. pneumoniae peritonitis/sepsis. This implies a compromised systemic, but not intracerebral host response against S. pneumoniae in MMP-9 deficiency.

Section snippets

Acknowledgements

The study was supported by a grant to T.B. from the Deutsche Akademie der Naturforscher Leopoldina, sponsored by the Federal Ministry for Education and Research, and by a grant to T.B. and R.N. from the Else Kröner-Fresenius Foundation.

References (18)

  • I. Azeh et al.

    Experimental pneumococcal meningitis in rabbits: the increase of matrix metalloproteinase-9 in cerebrospinal fluid correlates with leukocyte invasion

    Neurosci. Lett.

    (1998)
  • A. Wellmer et al.

    Spatial memory and learning deficits after experimental pneumococcal meningitis in mice

    Neurosci. Lett.

    (2000)
  • J. Allport et al.

    Neutrophils from MMP-9 or neutrophil elastase-deficient mice show no defect in transendothelial migration under flow in vitro

    J. Leukocyte Biol.

    (2002)
  • H. Echchannaoui et al.

    TLR2 deficient mice are highly susceptible to Streptococcus pneumoniae meningitis because of reduced bacterial clearing and enhanced inflammation

    J. Infect. Dis.

    (2002)
  • J. Ernst et al.

    Experimental pneumococcal meningitis: role of leukocytes in pathogenesis

    Infect. Immun.

    (1983)
  • J. Gerber et al.

    A mouse model of Streptococcus pneumoniae meningitis mimicking several features of human disease

    Acta Neuropathol. (Berlin)

    (2001)
  • B. Kieseier et al.

    Differential expression of matrix metalloproteinases in bacterial meningitis

    Brain

    (1999)
  • S. Leib et al.

    Matrix metalloproteinases contribute to brain damage in Experimental Pneumococcal Meningitis

    Infect. Immun.

    (2000)
  • S. Leib et al.

    Inhibition of matrix metalloproteinases and tumour necrosis factor alpha converting enzyme as adjuvant therapy in pneumococcal meningitis

    Brain

    (2001)
There are more references available in the full text version of this article.

Cited by (0)

View full text
Copyright © 2002 Published by Elsevier Ireland Ltd.