title: Bacterial hydrogen peroxide contributes to cerebral hyperemia during early stages of experimental pneumococcal meningitis.
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 (H(2)O(2)) because of the absence of functional catalase. In a 6 h rat model of experimental meningitis, we studied the impact of bacterial H(2)O(2) 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 H(2)O(2) 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 H(2)O(2)-degrading catalase or with tetraethylammonium (TEA), a blocker of calcium-sensitive potassium channels, which mediate H(2)O(2)-induced vasodilation. Catalase did not significantly reduce the remaining rCBF increase caused by SpxB(-), supporting the predominant role of bacterial H(2)O(2). We conclude that in addition to host-sided mediators, bacterial-derived H(2)O(2) acts as a potent vasodilator, which accounts for a certain proportion of the early cerebral hyperperfusion in pneumococcal meningitis.
authors.affiliation: Department of Experimental Neurology, Center for Anatomy, Charité-Universitaetsmedizin Berlin, Berlin, Germany. joerg.weber@charite.de
authors.forename: Olaf M
authors.initials: OM
authors.lastname: Hoffmann
authors.forename: Doreen
authors.initials: D
authors.lastname: Becker
authors.forename: Joerg R
authors.initials: JR
authors.lastname: Weber
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002374:Catalase / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006940:Hyperemia / Q000382:microbiology / Q000503:physiopathology*; D007427:Intracranial Pressure / Q000187:drug effects / Q000502:physiology; D008297:Male; D008586:Meningitis, Pneumococcal / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013296:Streptococcus pneumoniae / Q000378:metabolism*; D019789:Tetraethylammonium / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D014665:Vasodilator Agents; D019789:Tetraethylammonium; D006861:Hydrogen Peroxide; D002374:Catalase