Reactive nitrogen species contribute to blood-labyrinth barrier disruptionin suppurative labyrinthitis complicating experimental pneumococcal meningitis in the rat

Sensorineural hearing damage is a frequent complication of bacterial mening itis, affecting as many as 30% of survivors of pneumococcal meningitis. The re is a substantial body of evidence that oxidants, such as reactive nitrog en species (RNS), are central mediators of brain damage in experimental bac terial meningitis. In the present study, we investigated whether RNS also c ontribute to the pathophysiology of suppurative labyrinthitis in our well-e stablished 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) disru ption as evidenced by increased Evens Blue extravasation. Furthermore, incr eased cochlear expression of endothelial nitric oxide synthase (eNOS) and i nducible nitric oxide synthase (iNOS) was detected by immunohistochemistry. Colocalization of iNOS and tyrosine nitration ia marker of RNS attack) ind icated that nitric oxide (NO) produced by iNOS contributes to oxidative coc hlear damage through the action of RNS. To determine the parhophysiological role of RNS in BLB disruption, rats. were treated with peroxynitrite scave ngers tMnTBAP 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 disr uption was significantly reduced compared with that in infected animals tre ated only with ceftriaxone. Therefore, we conclude that RNS are involved in the breaching of the BLB during meningogenic pneumococcal labyrinthitis. ( C) 2001 Elsevier Science B.V. All rights reserved.