Serum matrix metalloproteinase-2 levels indicate blood-CSF barrier damage in patients with infectious meningitis.

OBJECTIVE: 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.

MATERIALS AND METHODS: 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).

RESULTS: 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).

CONCLUSION: Markedly increased levels of serum MMP-2 in infectious, especially bacterial, meningitis may reflect the degree of damage to the BCB.