Reactive nitrogen species contribute to blood-labyrinth barrier disruption in suppurative labyrinthitis complicating experimental pneumococcal meningitis in the rat.
Sensorineural hearing damage is a frequent complication of bacterial meningitis, affecting as many as 30% of survivors of pneumococcal meningitis. There is a substantial body of evidence that oxidants, such as reactive nitrogen species (RNS), are central mediators of brain damage in experimental bacterial meningitis. In the present study, we investigated whether RNS also contribute to the pathophysiology of suppurative labyrinthitis in our well-established rat model of pneumococcal meningitis. In all infected rats, but not in uninfected controls, we observed suppurative labyrinthitis. Cochlear inflammation was accompanied by severe blood-labyrinth barrier (BLB) disruption as evidenced by increased Evans Blue extravasation. Furthermore, increased cochlear expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) was detected by immunohistochemistry. Colocalization of iNOS and tyrosine nitration (a marker of RNS attack) indicated that nitric oxide (NO) produced by iNOS contributes to oxidative cochlear damage through the action of RNS. To determine the pathophysiological role of RNS in BLB disruption, rats were treated with peroxynitrite scavengers (MnTBAP and uric acid, UA). Six h after adjunctive treatment with 300 mg/kg i.p. UA or 15 mg/kg i.p. MnTBAP+100 mg/kg i.p. ceftriaxone, BLB disruption was significantly reduced compared with that in infected animals treated only with ceftriaxone. Therefore, we conclude that RNS are involved in the breaching of the BLB during meningogenic pneumococcal labyrinthitis.
Kastenbauer
S
S
Department of Neurology, Klinikum Grossetahadern, Ludwig-Maximilians University, Munich, Germany.
Klein
M
M
Koedel
U
U
Pfister
H W
HW
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D007758:Ear, Inner / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology*; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D007762:Labyrinthitis / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology; D008297:Male; D008586:Meningitis, Pneumococcal / Q000150:complications / Q000188:drug therapy / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000502:physiology*; D013492:Suppuration / Q000188:drug therapy / Q000201:enzymology
D016166:Free Radical Scavengers; D026361:Reactive Nitrogen Species; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat