Protective effect of the antioxidant N-acetyl-L-cysteine in pneumococcal meningitis in the rat.

We investigated whether the antioxidant N-acetyl-L-cysteine or S-methylisothiourea, an inhibitor of the inducible nitric oxide (NO) synthase, can modulate pathophysiological alterations in an advanced phase of experimental pneumococcal meningitis in the rat. N-acetyl-L-cysteine significantly attenuated the increase in brain water content, intracranial pressure and cerebrospinal fluid white blood cell count 24 h after infection as compared to untreated, infected rats. However, it had no effect on meningitis-associated disturbances in cerebrovascular autoregulation and CO2 reactivity of cerebral vessels. Treatment with S-methylisothiourea had no effect on the pathophysiological parameters measured in this model. These data suggest that reactive oxygen species, but not NO generated by the inducible NO synthase pathway, are key mediators of changes in brain water content, intracranial pressure and meningeal inflammation in an advanced stage of pneumococcal meningitis in the rat.