Serum Matrix Metalloproteinase-2 Levels Indicate Blood–CSF Barrier Damage in Patients with Infectious Meningitis

Abstract

Protein components in cerebrospinal fluid (CSF) are maintained at a specific concentration by a dynamic gradient between the capillary and intrathecal spaces via the blood-cerebrospinal fluid barrier (BCB) in the brain and spinal cord. Permeability to proteins increases when there is structural damage to the BCB. Matrix metalloproteinase-2 (MMP-2; gelatinase A) has been shown to degrade type IV collagen, a major component of the cellular basement membrane. We analyzed alpha2 macroglobulin (alpha2M) indices and evaluated the relationship between alpha2M, as an indicator of BCB permeability, and MMP-2, which degrades the extra-cellular matrix in patients with infectious meningitis. Albumin levels in CSF or serum were determined by turbidimetric immunoassay, or bromcresol green assay, respectively. alpha2M levels in CSF or serum were measured with enzyme-linked immunosorbent assay, or laser-nephelometry, respectively. Serum MMP-2 levels were determined by enzyme immuno assay. We calculated the alpha2M index, i.e. the ratio of alpha2M (CSF / serum) to albumin (CSF / serum; alpha2M in CSF / alpha2M in serum x albumin in serum / albumin in CSF). alpha2M indices were significantly increased in infectious meningitis compared to healthy controls (p < 0.05). They were highest in bacterial meningitis, and there was a significant difference between viral or mycotic and bacterial meningitis (p < 0.05). Serum MMP-2 levels were increased in infectious meningitis, being highest in bacterial meningitis, where they were significantly different from healthy controls (p < 0.05). There was a significant positive correlation between serum MMP-2 levels and alpha2M indices (r = 0.64, p < 0.0001). Markedly increased levels of serum MMP-2 in infectious, especially bacterial, meningitis may reflect the degree of damage to the BCB.