Objective: To determine whether peoxynitrite (P) is involved in mediating brain injury (BI) in bacterial meningitis (BM). Background: P is a strong oxidant produced by the reaction of superoxide anion (O) with nitric oxide (NO) in vivo, which may cause neuronal cell damage and death by multiple mechanisms. P inhibits mitochondrial (M) respiration; causes M calcium efflux and depolarization; and induces DNA strand breaks with activation of poly(ADP ribose) synthetase (PARS), a reaction which may deplete intracellular NAD+ and ATP. Because O and NO have been shown to be important mediators of BI in BM, compounds which bind or inhibit the effect of P were tested: uric acid (UA), a P scavenger and 3-aminobenzamide (AB), a specific PARS inhibitor. Methods: An infant rat model of Group B Streptococcal (GBS) BM was used (Kim YS et al 1995). Five groups of 11d old rats were studied: uninfected; infected (I); I + UA(10mg/kg/ip tid); I + AB (10mg/kg/ip bid); and I + UA + AB. UA and AB were given 6h before infection. Rats were infected by intracisternal injection of log 4.0 GBS. 15h post infection (PI), quantitative CSF bacterial titer determined by serial dilution. 18h PI, animals were sacrificed and brains fixed. Neuronal injury was determined by scoring Nissl-stained brain sections. The presence of P was determined by staining for nitrotyrosine (NT), a specific nitration product of P, in sections incubated with poly anti-NT IgG(courtesy J Beckmann, U Alabama Birmingham). Results are shown below as X +/- SD or #/#. Conclusions: Combined UA and AB treatment attenuated BI in this model of BM, suggesting that P may be a mediator of injury in this disease. UA was effective in reducing + NT stain. Table

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