Matrix metalloproteinases contribute to the blood—brain barrier disruption during bacterial meningitis
- 8 October 1998
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 44 (4), 592-600
- https://doi.org/10.1002/ana.410440404
Abstract
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.Keywords
This publication has 42 references indexed in Scilit:
- 7-Nitroindazole Inhibits Pial Arteriolar Vasodilation in a Rat Model of Pneumococcal MeningitisJournal of Cerebral Blood Flow & Metabolism, 1997
- Treatment of Bacterial MeningitisNew England Journal of Medicine, 1997
- Increased Production of Matrix Metalloproteinases in Enriched Astrocyte and Mixed Hippocampal Cultures Treated with β‐Amyloid PeptidesJournal of Neurochemistry, 1996
- Tumor necrosis factor-α-induced gelatinase B causes delayed opening of the blood-brain barrier: an expanded therapeutic windowBrain Research, 1995
- Nitric Oxide Activates Metalloprotease Enzymes in Articular CartilageBiochemical and Biophysical Research Communications, 1995
- Inhibition of the metastatic spread and growth of B16‐BL6 murine melanoma by a synthetic matrix metalloproteinase inhibitorInternational Journal of Cancer, 1994
- Antioxidants attenuate microvascular changes in the early phase of experimental pneumococcal meningitis in rats.Stroke, 1992
- Bacterial Meningitis: Pathogenesis, Pathophysiology, and ProgressNew England Journal of Medicine, 1992
- Substances that rapidly augment ionic conductance of endothelium in cerebral venulesActa Physiologica Scandinavica, 1986
- BASEMENT MEMBRANE SURFACES AND PERIVASCULAR COMPARTMENTS IN NORMAL HUMAN BRAIN AND GLIAL TUMOURS. A SCANNING ELECTRON MICROSCOPE STUDYNeuropathology and Applied Neurobiology, 1983