Matrix Metalloproteinase (MMP)-8 and MMP-9 in Cerebrospinal Fluid during Bacterial Meningitis: Association with Blood-Brain Barrier Damage and Neurological Sequelae

• Published in: Clinical infectious diseases Vol. 31; no. 1; pp. 80 - 84
• Main Authors: Leppert, D., Leib, S. L., Grygar, C., Miller, K. M., Schaad, U. B., Holländer, G. A.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01-07-2000; University of Chicago Press
• Subjects: Bacterial diseases; Bacterial diseases of the nervous system. Bacterial myositis; Bacterial meningitis; Biological and medical sciences; Blood brain barrier; Brain damage; Brain Damage, Chronic - cerebrospinal fluid; Brain Damage, Chronic - pathology; Cerebrospinal fluid; Child; Child, Preschool; Clinical Articles; Corticosteroids; Follow-Up Studies; Granulocytes; Haemophilus Infections - cerebrospinal fluid; Haemophilus Infections - pathology; Haemophilus influenzae; Human bacterial diseases; Humans; Infant; Infectious diseases; Lumbar punctures; Matrix Metalloproteinase 2 - cerebrospinal fluid; Matrix Metalloproteinase 3 - cerebrospinal fluid; Matrix Metalloproteinase 8 - cerebrospinal fluid; Matrix Metalloproteinase 9 - cerebrospinal fluid; Medical sciences; Meningitis, Bacterial - cerebrospinal fluid; Meningitis, Bacterial - pathology; Meningitis, Meningococcal - cerebrospinal fluid; Meningitis, Meningococcal - pathology; Meningitis, Pneumococcal - cerebrospinal fluid; Meningitis, Pneumococcal - pathology; Necrosis; Neisseria meningitidis; Nervous system diseases; Retrospective Studies; Spinal Puncture; Streptococcus pneumoniae; Time Factors; Tissue Inhibitor of Metalloproteinase-1 - cerebrospinal fluid; Tissue Inhibitor of Metalloproteinase-2 - cerebrospinal fluid; Tumor Necrosis Factor-alpha - analysis; Up regulation; Human; Nervous system diseases; Correlation; Enzyme; Enzyme inhibitor; Metalloendopeptidases; Infant; Sequela; Cerebrospinal fluid; Blood brain barrier; Gelatinase B; Retrospective; Infection; Peptidases; Central nervous system disease; Neutrophil collagenase; Bacteriosis; Hydrolases; Complication; Meningitis; Child; Gravity
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/313922

To evaluate the spectrum and regulation of matrix metalloproteinases (MMPs) in bacterial meningitis (BM), concentrations of MMP-2, MMP-3, MMP-8, and MMP-9 and endogenous inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were measured in the cerebrospinal fluid (CSF) of 27 children with BM. MMP-8 and MMP-9 were detected in 91% and 97%, respectively, of CSF speci-mens from patients but were not detected in control patients. CSF levels of MMP-9 were higher (P <.05) in 5 patients who developed hearing impairment or secondary epilepsy than in those who recovered without neurological deficits. Levels of MMP-9 correlated with concentrations of TIMP-1 (P <.001) and tumor necrosis factor-α (P =.03). Repeated lumbar punctures showed that levels of MMP-8 and MMP-9 were regulated independently and did not correlate with the CSF cell count. Therefore, MMPs may derive not only from granulocytes infiltrating the CSF space but also from parenchymal cells of the meninges and brain. High concentrations of MMP-9 are a risk factor for the development of postmeningitidal neurological sequelae.