Marked increase of matrix metalloproteinase 9 in cerebrospinal fluid of patients with fungal or tuberculous meningoencephalitis

Eiji Matsuura, Fujio Umehara, Teruto Hashiguchi, Noboru Fujimoto, Yasunori Okada, Mitsuhiro Osame

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74 Citations (Scopus)


Matrix metalloproteinases (MMPs) are believed to play an essential role in the breakdown of the extracellular matrix macromolecules in the blood-cerebrospinal fluid barrier and blood-brain barrier (BBB). In this study, the levels of MMP-2 and MMP-9 and their common tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were measured in the cerebrospinal fluid (CSF) from patients with various meningitides including aseptic, fungal and tuberculous ones. MMP-9 production level in CSF was more increased in subacute meningitis including fungal and tuberculous meningitis than in acute aseptic meningitis and non-inflammatory neurological diseases (NIDs). Enhanced production of MMP-9 was associated with high proteolytic activity detected by gelatin zymography. The MMP-2 and TIMP-1 levels in CSF of subacute meningitis were also higher than those of NIDs. In contrast, the TIMP-2 levels in CSF of either acute aseptic or subacute meningitis were not up-regulated compared with those of NIDs. The central nervous system (CNS) complications (i.e. disturbance of consciousness, psychiatric symptoms, urinary disturbance, etc.) during the course of meningitis showed good correlation with the enhanced production of MMP-9 in CSF. Immunohistochemical studies in tuberculous meningitis demonstrated that the infiltrating mononuclear cells in the meninges were immunoreactive for both MMP-2 and MMP-9. However, the infiltrating mononuclear cells into CNS parenchyma had immunoreactivity for MMP-9, but not for MMP-2. Taken together, those data suggest that MMP-9 in CSF may be a useful marker of encephalitogenecity during the course of subacute meningitis. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)45-52
Number of pages8
JournalJournal of the Neurological Sciences
Issue number1
Publication statusPublished - 2000 Feb 1


  • Aseptic meningitis
  • Cerebrospinal fluid
  • Matrix metalloproteinase 9
  • Tissue inhibitor of metalloproteinases 1
  • Tuberculous meningitis

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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