Bacterial hydrogen peroxide contributes to cerebral hyperemia during early stages of experimental pneumococcal meningitis

Alterations of blood flow contribute to major clinical complications in invasive infections such as sepsis and bacterial meningitis. As a unique feature streptococci - in particular, Streptococcus pneumoniae, the most frequent pathogen in bacterial meningitis - release hydrogen peroxide ( H2O2) because of the absence of functional catalase. In a 6 h rat model of experimental meningitis, we studied the impact of bacterial H2O2 production on regional cerebral blood flow ( rCBF) and intracranial pressure (ICP). Compared to wild- type D39 pneumococci, the increase of rCBF was diminished in meningitis induced by the H2O2 defective SpxB- mutant ( maximum increase, 135% +/- 17% versus 217% +/- 23% of the individual baseline; P< 0.01) or after treatment of D39- induced meningitis with H2O2- degrading catalase or with tetraethylammonium ( TEA), a blocker of calciumsensitive potassium channels, which mediate H2O2- induced vasodilation. Catalase did not significantly reduce the remaining rCBF increase caused by SpxB-, supporting the predominant role of bacterial H2O2. We conclude that in addition to host- sided mediators, bacterial- derived H2O2 acts as a potent vasodilator, which accounts for a certain proportion of the early cerebral hyperperfusion in pneumococcal meningitis.