Oxidative stress in brain during experimental bacterial meningitis: differential effects of alpha-phenyl-tert-butyl nitrone and N-acetylcysteine treatment.
Antioxidant treatment has previously been shown to be neuroprotective in experimental bacterial meningitis. To obtain quantitative evidence for oxidative stress in this disease, we measured the major brain antioxidants ascorbate and reduced glutathione, and the lipid peroxidation endproduct malondialdehyde in the cortex of infant rats infected with Streptococcus pneumoniae. Cortical levels of the two antioxidants were markedly decreased 22 h after infection, when animals were severely ill. Total pyridine nucleotide levels in the cortex were unaltered, suggesting that the loss of the two antioxidants was not due to cell necrosis. Bacterial meningitis was accompanied by a moderate, significant increase in cortical malondialdehyde. While treatment with either of the antioxidants alpha-phenyl-tert-butyl nitrone or N-acetylcysteine significantly inhibited this increase, only the former attenuated the loss of endogenous antioxidants. Cerebrospinal fluid bacterial titer, nitrite and nitrate levels, and myeloperoxidase activity at 18 h after infection were unaffected by antioxidant treatment, suggesting that they acted by mechanisms other than modulation of inflammation. The results demonstrate that bacterial meningitis is accompanied by oxidative stress in the brain parenchyma. Furthermore, increased cortical lipid peroxidation does not appear to be the result of parenchymal oxidative stress, because it was prevented by NAC, which had no effect on the loss of brain antioxidants.
Christen
S
S
Institute for Infectious Diseases, University of Berne, Berne, Switzerland. stephan.christen@ifik.unibe.ch
Schaper
M
M
Lykkesfeldt
J
J
Siegenthaler
C
C
Bifrare
Y D
YD
Banic
S
S
Leib
S L
SL
Täuber
M G
MG
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002555:Cerebrospinal Fluid / Q000382:microbiology; D003497:Cyclic N-Oxides; D004195:Disease Models, Animal; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000134:cerebrospinal fluid; D008586:Meningitis, Pneumococcal / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013296:Streptococcus pneumoniae / Q000254:growth & development
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D009589:Nitrogen Oxides; C029217:phenyl-N-tert-butylnitrone; D005978:Glutathione; D000111:Acetylcysteine