Matrix metalloproteinases contribute to brain damage in experimental pneumococcal meningitis

Leib, Stephen L.; Leppert, David; Clements, John; Täuber, Martin G. (2000). Matrix metalloproteinases contribute to brain damage in experimental pneumococcal meningitis. Infection and immunity, 68(2), pp. 615-620. New York, N.Y.: American Society for Microbiology 10.1128/IAI.68.2.615-620.2000

[img] Text
Infect. Immun.-2000-Leib-615-20.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (802kB) | Request a copy

The present study was performed to evaluate the role of matrix metalloproteinases (MMP) in the pathogenesis of the inflammatory reaction and the development of neuronal injury in a rat model of bacterial meningitis. mRNA encoding specific MMPs (MMP-3, MMP-7, MMP-8, and MMP-9) and the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) were significantly (P < 0.04) upregulated, compared to the beta-actin housekeeping gene, in cortical homogenates at 20 h after infection. In parallel, concentrations of MMP-9 and TNF-alpha in cerebrospinal fluid (CSF) were significantly increased in rats with bacterial meningitis compared to uninfected animals (P = 0.002) and showed a close correlation (r = 0.76; P < 0. 001). Treatment with a hydroxamic acid-type MMP inhibitor (GM6001; 65 mg/kg intraperitoneally every 12 h) beginning at the time of infection significantly lowered the MMP-9 (P < 0.02) and TNF-alpha (P < 0.02) levels in CSF. Histopathology at 25.5 +/- 5.7 h after infection showed neuronal injury (median [range], 3.5% [0 to 17.5%] of the cortex), which was significantly (P < 0.01) reduced to 0% (0 to 10.8%) by GM6001. This is the first report to demonstrate that MMPs contribute to the development of neuronal injury in bacterial meningitis and that inhibition of MMPs may be an effective approach to prevent brain damage as a consequence of the disease.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

UniBE Contributor:

Leib, Stephen and Täuber, Martin G.

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0019-9567

ISBN:

10639424

Publisher:

American Society for Microbiology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:00

Last Modified:

11 Jan 2015 01:22

Publisher DOI:

10.1128/IAI.68.2.615-620.2000

PubMed ID:

10639424

Web of Science ID:

000084842000025

BORIS DOI:

10.7892/boris.25754

URI:

https://boris.unibe.ch/id/eprint/25754 (FactScience: 60877)

Actions (login required)

Edit item Edit item
Provide Feedback