Matrix metalloproteinase-9 (MMP-9) in human cerebrospinal fluid (CSF): elevated levels are primarily related to CSF cell count

Abstract

Matrix metalloproteinase-9 (MMP-9) was investigated by enzyme-linked immunosorbent assay (ELISA) and zymography in 111 paired CSF and serum samples from patients with various neurological disorders. In 20 patients with blood–brain barrier (BBB) impairment but normal CSF cell count, elevated levels of MMP-9 were not observed by ELISA measurement. Another 11 patients characterized in the same way, exhibited only slightly increased MMP-9 levels. In contrast, in 12 patients with intact BBB but elevated CSF cell count, MMP-9 was increased too. It was shown by the more sensitive zymography that MMP-9 increased if CSF cell count exceeded five cells per μl. Spearman rank statistics revealed that MMP-9 concentration in CSF correlated with CSF cell count ( r=0.755; P<0.0001), but not with CSF/serum albumin ratio ( Q Alb) ( r=0.212; P=0.057), a measure for BBB impairment. Moreover, the CSF/serum MMP-9 ratio ( Q MMP-9) did not correlate with Q Alb( r=0.192; P=0.100). By use of a Boyden chamber, in which granulocytes migrated through a reconstituted basement membrane, it was demonstrated that the MMP-9 concentration in the lower chamber correlated very significantly with the number of accumulated cells ( r 2=0.7692; P<0.0001). The meaning of the increase of MMP-9 in CSF is critically discussed.