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In parallel, concentrations of MMP-9 and TNF-\u03b1 in cerebrospinal fluid (CSF) were significantly increased in rats with bacterial meningitis compared to uninfected animals (<jats:italic>P<\/jats:italic>= 0.002) and showed a close correlation (<jats:italic>r<\/jats:italic>= 0.76;<jats:italic>P<\/jats:italic>&lt; 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 (<jats:italic>P<\/jats:italic>&lt; 0.02) and TNF-\u03b1 (<jats:italic>P<\/jats:italic>&lt; 0.02) levels in CSF. Histopathology at 25.5 \u00b1 5.7 h after infection showed neuronal injury (median [range], 3.5% [0 to 17.5%] of the cortex), which was significantly (<jats:italic>P<\/jats:italic>&lt; 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.<\/jats:p>","DOI":"10.1128\/iai.68.2.615-620.2000","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:03:59Z","timestamp":1027764239000},"page":"615-620","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":215,"title":["Matrix Metalloproteinases Contribute to Brain Damage in Experimental Pneumococcal Meningitis"],"prefix":"10.1128","volume":"68","author":[{"given":"Stephen L.","family":"Leib","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Institute for Medical Microbiology, University of Berne, Berne,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Leppert","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Departments of Research and Neurology, University Hospitals, Basel,2 Switzerland, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Clements","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->British Biotech Pharmaceuticals plc, Oxford, United Kingdom3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin G.","family":"Ta\u0308uber","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Institute for Medical Microbiology, University of Berne, Berne,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00032-3"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1997.tb01315.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(98)00046-0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.102.5.1087"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(98)00776-9"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.1677"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(96)00179-8"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(96)00210-X"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004310051056"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.66041641.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(97)00380-7"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00309339"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00856807"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1994.tb24746.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/370555a0"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117578"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1159\/000097229"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1754.1996.tb00949.x"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(96)12837-8"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1995.tb31402.x"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/122.8.1579"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199507000-00007"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(97)00247-6"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119084"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/173.1.166"},{"key":"e_1_3_2_27_2","unstructured":"Leib S. 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