Role of peroxynitrite as a mediator of pathophysiological alterations in experimental pneumococcal meningitis.
This study investigated the role of peroxynitrite in an adult rat model of pneumococcal meningitis. Immunohistochemically, nitrotyrosine residues, as a marker for peroxynitrite formation, were detected perivascularly and in proximity to inflammatory cells in the subarachnoid space. Nitrotyrosine immunoreactivity was colocalized with blood-brain barrier breaching, which was visualized by fluorescence microscopy after intravenous application of Evans blue. Treatment of infected rats with uric acid (300 mg/kg intraperitoneally), a scavenger of peroxynitrite, significantly attenuated intracranial pressure, cerebrospinal fluid white blood cell count, and blood-brain barrier leakage, as indicated by Evans blue concentration in the cerebrospinal fluid (21.6+/-9.3 mm Hg, 5776+/-1790 cells/microL, 9.7+/-6.4 microgram/mL in infected, untreated rats vs. 7.2+/-1.6 mm Hg, 2004+/-904 cells/microL, 1.1+/-1.0 microgram/mL infected, uric acid-treated rats, mean+/-SD, P<.05). These data suggest that peroxynitrite plays a central role in mediating pathophysiological alterations during bacterial meningitis.
Kastenbauer
S
S
Department of Neurology, Grosshadern Clinic, Ludwig-Maximilians-University, 81377 Munich, Germany.
Koedel
U
U
Pfister
H W
HW
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D007249:Inflammation; D007427:Intracranial Pressure / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D008586:Meningitis, Pneumococcal / Q000134:cerebrospinal fluid / Q000473:pathology / Q000503:physiopathology*; D009566:Nitrates / Q000502:physiology*; D016877:Oxidants / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013346:Subarachnoid Space; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D014527:Uric Acid / Q000494:pharmacology
D016166:Free Radical Scavengers; D009566:Nitrates; D016877:Oxidants; C039642:peroxynitric acid; D014527:Uric Acid; C002744:3-nitrotyrosine; D014443:Tyrosine