Matrix metalloproteinase (MMP)-8 and MMP-9 in cerebrospinal fluid during bacterial meningitis: association with blood-brain barrier damage and neurological sequelae.
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 specimens 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-alpha (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.
Departments of Research and Neurology, University Hospitals, CH-4031 Basel, Switzerland. David.Leppert@.unibas.ch
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D
Leppert
S L
SL
Leib
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Grygar
K M
KM
Miller
U B
UB
Schaad
G A
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Holländer
D001812:Blood-Brain Barrier; D001925:Brain Damage, Chronic / Q000134:cerebrospinal fluid* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005500:Follow-Up Studies; D006192:Haemophilus Infections / Q000134:cerebrospinal fluid* / Q000473:pathology; D006193:Haemophilus influenzae; D006801:Humans; D007223:Infant; D020778:Matrix Metalloproteinase 2 / Q000134:cerebrospinal fluid; D019278:Matrix Metalloproteinase 3 / Q000134:cerebrospinal fluid; D020784:Matrix Metalloproteinase 8 / Q000134:cerebrospinal fluid*; D020780:Matrix Metalloproteinase 9 / Q000134:cerebrospinal fluid*; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid* / Q000473:pathology; D008585:Meningitis, Meningococcal / Q000134:cerebrospinal fluid* / Q000473:pathology; D008586:Meningitis, Pneumococcal / Q000134:cerebrospinal fluid* / Q000473:pathology; D009345:Neisseria meningitidis; D012189:Retrospective Studies; D013129:Spinal Puncture; D013296:Streptococcus pneumoniae; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000134:cerebrospinal fluid; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000134:cerebrospinal fluid; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D019716:Tissue Inhibitor of Metalloproteinase-2; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9