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Matrix metalloproteinases contribute to the blood—brain barrier disruption during bacterial meningitis
Author(s) -
Paul Robert,
Lorenzl Stefan,
Koedel Uwe,
Sporer Bernd,
Vogel Ulrich,
Frosch Matthias,
Pfister HansWalter
Publication year - 1998
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410440404
Subject(s) - meningitis , cerebrospinal fluid , pleocytosis , blood–brain barrier , medicine , white blood cell , matrix metalloproteinase , neisseria meningitidis , immunology , meningococcal meningitis , pathology , central nervous system , biology , bacteria , surgery , genetics
In this study, we investigated the involvement of matrix metalloproteinases (MMPs) in the pathophysiology of bacterial meningitis. By using an enzyme immunoassay, high concentrations of MMP‐9 were detected in the cerebrospinal fluid (CSF) of adult patients with bacterial meningitis but not in controls, and in patients with Guilain‐Barré syndrome. Moreover, we observed significantly elevated concentrations of the tissue inhibitor of metalloproteinase‐1 (TIMP‐1) in the CSF of patients with bacterial meningitis, compared with controls. In a rat model of meningococcal meningitis, intracisternal injection of heat‐killed meningococci caused a disruption of the blood–;brain barrier (BBB), and increase in intracranial pressure, and CSF pleocytosis paralleled by the occurrence of MMP‐9 activity in the CSF 6 hours after meningococcal challenge. The MMP inhibitor batimastat (BB‐94) significantly reduced the BBB disruption and the increase in intracranial pressure irrespective of the time of batmastat administration (15 minutes before and 3 hours after meningococcal challenge) but failed to significantly reduce CSF white blood cell counts. In conclusion, our results suggest that MMPs are involved in the alterations of BBB permeability during experimental meningococcal meningitis.