Protective effect of a 21-aminosteroid during experimental pneumococcal meningitis.
This study investigated whether the 21-aminosteroid U74389F, an inhibitor of lipid peroxidation, attenuates pathophysiologic changes in experimental pneumococcal meningitis. Infected rats injected intravenously with vehicle of [corrected] U74389F developed increases in regional cerebral blood flow (rCBF), intracranial pressure (ICP), brain water content, and white blood cells (WBC) in cerebrospinal fluid (CSF) within 8 h after intracisternal challenge. Pretreatment with or administration of U74389F 4 h after infection significantly reduced the increase in ICP but had no effect on rCBF increase. Moreover, U74389F pretreatment significantly reduced brain water content and CSF WBC count. In vitro, U74389F inhibited iron-dependent lipid peroxidation of astrocyte cultures and the production of tumor necrosis factor-alpha, interleukin-6, and nitric oxide by stimulated macrophages. These data suggest that U74389F modulates early pathophysiologic alterations in experimental pneumococcal meningitis.
Lorenzl
S
S
Department of Neurology, Klinikum Grosshadern Ludwig-Maximilians-University of Munich, Germany.
Koedel
U
U
Frei
K
K
Bernatowicz
A
A
Fontana
A
A
Pfister
H W
HW
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid / Q000166:cytology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D007427:Intracranial Pressure / Q000187:drug effects; D007501:Iron / Q000494:pharmacology; D007958:Leukocyte Count / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology; D008297:Male; D008586:Meningitis, Pneumococcal / Q000503:physiopathology* / Q000517:prevention & control*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011281:Pregnatrienes / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000975:Antioxidants; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011281:Pregnatrienes; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C074965:U 74389F; D009569:Nitric Oxide; D007371:Interferon-gamma; D007501:Iron