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Assessment of hydroxyproline as a marker for collagenolytic activity in neuroinflammatory disorders

Abstract number: 1134_02_152

Sellner J., Simon F., Meli D., Grandgirard D., Storch-Hagenlocher B., Meyding-Lamade U., Leib S.

Objectives:

Pathophysiologic mechanisms that contribute to brain injury in neuroinflammatory disorders include breakdown of the blood-brain-barrier, extravasation of leukocytes, cerebral hypoperfusion and vasculitis. Matrix-Metalloproteinases (MMPs) including the collagenases MMP-2 and -9 are crucially involved in all these steps. In this study we aimed to assess the extent of in-vivo collagenolytic activity in cerebrospinal fluid (CSF) by determination of the amino acid hydroxyproline, a major and exclusive degradation product of collagen.

Methods:

Paired serum and CSF samples from patients with bacterial meningitis (n = 11), aseptic meningitis/encephalitis (n = 17), multiple sclerosis (n = 13), and normal CSF (n = 12) were assessed. Degraded collagen was hydrolysed to dissolve its major component hydroxyproline, which subsequently was determined spectrophotometrically. CSF levels of MMP-2 and -9 were studied by gel zymography. In a rat model of pneumococcal meningitis localization of collagenolytic activity was performed by in-situ zymography with intramolecularly quenched gelatin.

Results:

Hydroxyproline in CSF from patients with bacterial meningitis was significantly increased compared to all studied groups (P < 0.001) while serum hydroxyproline did not differ significantly between the groups. The amount of hydroxyproline in CSF correlated significantly with the amount of MMP-9 (r = 0.8; p < 0.001). In the rat model in-situ zymography localized gelatinolytic activity to the subarachnoidal and ventricular space inflammation and in association to cortical lesions.

Summary & Conclusions:

The study documents a significant increase of the collagen degradation product hydroxyproline in CSF of patients with bacterial meningitis. The close correlation of hydroxyproline and MMP-9 in the CSF validates the assessment of hydroxyproline as an index for CSF collagenolytic activity in neuroinflammatory diseases and supports a role for collagenases in the pathogenesis of bacterial meningitis.

Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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