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 M MP-8 and endogenous inhibitors of metalloproteinases (TIMP-1 and TIMP-2) we re 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 we re higher (P < .05) in 5 patients who developed hearing impairment or secon dary epilepsy than in those who recovered without neurological deficits. Le vels of MMP-9 correlated with concentrations of TIMP-1 (P < .001) and tumor necrosis factor-ac (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 developme nt of postmeningitidal neurological sequelae.