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Compared to untreated infected rats, superoxide dismutase given 3 hours after infection significantly attenuated the increase of brain water content, intracranial pressure, and cerebrospinal fluid white blood cell count, but did not modulate the increase in regional cerebral blood flow. N\u2010Nitro\u2010L\u2010arginine treatment (5 mg\/kg intravenously, followed by 5 mg\/kg\/hour) reversed the increase in regional cerebral blood flow; prevented an increase in brain water content, intracranial pressure, and cerebrospinal fluid nitrite concentrations; and reduced cerebrospinal fluid white blood cell count. With a closed cranial window preparation, N\u2010nitro\u2010L\u2010arginine prevented pneumococci\u2010induced dilatation of pial arterioles. When the effective dose was increased twofold, the effects of N\u2010nitro\u2010Lvarginine became more pronounced but resulted in the death of 4 of 5 rats, probably due to hemodynamic side effects. In primary cultures of rat cerebral endothelial cells, nitrite concentrations increased after pneumococcal stimulation, which could be prevented by NvnitrovLvarginine and cycloheximide. These data suggest that (a) nitric oxide accounts for regional cerebral blood flow changes and pial arteriolar dilatation in the early phase of experimental pneumococcal meningitis; (b) both superoxide radical and nitric oxide are involved as mediators of brain edema and meningeal inflammation; and (c) cerebral endothelial cells can be stimulated by pneumococci to release nitric oxide presumably via the inducible nitric oxide synthase.<\/jats:p>","DOI":"10.1002\/ana.410370307","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T16:14:15Z","timestamp":1104596055000},"page":"313-323","source":"Crossref","is-referenced-by-count":115,"title":["Experimental pneumococcal meningitis: Cerebrovascular alterations, brain edema, and meningeal inflammation are linked to the production of nitric oxide"],"prefix":"10.1002","volume":"37","author":[{"given":"Uwe","family":"Koedel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Bernatowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Frei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Fontana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans\u2010Walter","family":"Pfister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,10,8]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199209173271208"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199301073280104"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1993.00540060015010"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114292"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115140"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1990.148"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199206000-00020"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/162.1.139"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.170.3.959"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197510022931407"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198902093200606"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410020202"},{"key":"e_1_2_1_14_2","first-page":"109","article-title":"Palmer RMJ, Higgs EA. 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