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 (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.
Hoffmann
Olaf M
OM
Department of Experimental Neurology, Center for Anatomy, Charité-Universitaetsmedizin Berlin, Berlin, Germany. joerg.weber@charite.de
Becker
Doreen
D
Weber
Joerg R
JR
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
D000975:Antioxidants; D014665:Vasodilator Agents; D019789:Tetraethylammonium; D006861:Hydrogen Peroxide; D002374:Catalase