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Differential expression of matrix metalloproteinases in bacterial meningitis
B C Kieseier1, R Paul, U Koedel
1Department of Neurology, Karl-Franzens-Universität, Graz, Austria, Department of Neurology, Ludwig-Maximilians-Universität, München, Germany. bc.kieseir@kfunigraz.ac.at
Abstract:
Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of various inflammatory diseases of the central nervous system. Evidence is accumulating that gelatinase B (MMP-9) might be involved in the pathogenesis of meningitis, but the spectrum of different MMPs involved in the inflammatory reaction of this disease has not been determined. We investigated the temporal and spatial mRNA expression pattern of gelatinase B in experimental meningococcal meningitis in rats. In contrast to controls, increased mRNA levels with peak values 6 h after injection with menigococci were found in brain specimens of the animals. Elevated MMP-9 mRNA expression was accompanied by enhanced proteolytic activity, as demonstrated by gelatin zymography, and positive immunoreactivity. The mRNA expression pattern of six other MMPs was investigated. Collagenase-3 and stromelysin-1 mRNAs were also found to be upregulated. In contrast, mRNA levels for gelatinase A, matrilysin, stromelysin-2 and stromelysin-3 remained unchanged. As evidenced by significantly increased intracranial pressure and by leakage of intravenously injected Evans blue through the blood vessel walls into the brain parenchyma, the animals injected with meningococci revealed signs of blood-brain barrier disruption. Augmented proteolytic activity of MMP-9 could also be demonstrated in CSF samples obtained from patients with bacterial meningitis, underlining the clinical relevance of our experimental findings. Our data indicate that gelatinase B, collagenase-3 and stromelysin-1 are selectively upregulated in bacterial meningitis and thus may contribute to the pathogenesis of this infectious disease of the central nervous system.
Insights
Matrix metalloproteinases (MMPs), specifically gelatinase B (MMP-9), collagenase-3, and stromelysin-1, are upregulated in bacterial meningitis. These MMPs may contribute to the central nervous system inflammation and blood-brain barrier disruption seen in this disease.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) play a role in central nervous system inflammatory diseases.
- Gelatinase B (MMP-9) is suspected in meningitis pathogenesis, but the full spectrum of MMPs involved is unknown.
Purpose of the Study:
- To investigate the temporal and spatial mRNA expression of gelatinase B (MMP-9) in experimental meningococcal meningitis.
- To determine the expression patterns of other MMPs during bacterial meningitis.
Main Methods:
- Experimental meningococcal meningitis model in rats.
- Analysis of mRNA expression using quantitative methods.
- Gelatin zymography and immunoreactivity assays to assess proteolytic activity.
- Measurement of intracranial pressure and blood-brain barrier permeability.
Main Results:
- MMP-9 mRNA levels significantly increased in rat brains post-meningococcal infection, peaking at 6 hours.
- Elevated MMP-9 expression correlated with increased proteolytic activity and blood-brain barrier disruption.
- Collagenase-3 and stromelysin-1 mRNA were also upregulated, while other MMPs remained unchanged.
- Increased MMP-9 activity was detected in cerebrospinal fluid (CSF) from human bacterial meningitis patients.
Conclusions:
- Gelatinase B (MMP-9), collagenase-3, and stromelysin-1 are selectively upregulated in bacterial meningitis.
- These MMPs likely contribute to the pathogenesis of meningitis and associated central nervous system inflammation.
- Findings highlight the clinical relevance of MMPs in bacterial meningitis.