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 ex perimental bacterial meningitis. To obtain quantitative evidence for oxidat ive stress in this disease, we measured the major brain antioxidants ascorb ate and reduced glutathione, and the lipid peroxidation endproduct malondia ldehyde in the cortex of infant rats infected with Streptococcus pneumoniae . Cortical levels of the two antioxidants were markedly decreased 22 h afte r infection, when animals were severely ill. Total pyridine nucleotide leve ls in the cortex were unaltered, suggesting that the loss of the two antiox idants was not due to cell necrosis. Bacterial meningitis was accompanied b y a moderate, significant increase in cortical malondialdehyde. While treat ment with either of the antioxidants alpha -phenyl-tert-butyl nitrone or N- acetylcysteine significantly inhibited this increase, only the former atten uated the loss of endogenous antioxidants. Cerebro-spinal fluid bacterial t iter, nitrite and nitrate levels, and myeloperoxidase activity at 18 h afte r infection were unaffected by antioxidant treatment, suggesting that they acted by mechanisms other than modulation of inflammation. The results demo nstrate 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. ( C) 2001 Elsevier Science Inc.