1. ¹Department of Experimental Neurology, Center for Anatomy, Charité-Universitaetsmedizin Berlin, Berlin, Germany
2. ²Department of Cell Biology and Neurobiology, Center for Anatomy, Charité-Universitaetsmedizin Berlin, Berlin, Germany

Correspondence: Dr JR Weber, Department of Cell Biology and Neurobiology, Center for Anatomy, Charité – Universitaetsmedizin Berlin, Charitéplatz 1, Berlin 10117, Germany. E-mail: joerg.weber@charite.de

Received 25 September 2006; Revised 16 January 2007; Accepted 16 January 2007; Published online 21 February 2007.

Abstract

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 calcium-sensitive 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.