ABSTRACT
Microperfusion of scala tympani with the NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP), produced marked depression of the compound action potential (CAP) and cochlear microphonic (CM) together with severe and widespread morphological damage to hair cells and supporting cells in the organ of Corti. In addition, direct perfusion of N-methyl-D-aspartate (NMDA) into scala tympani, which probably induces excess stimulation of NMDA receptors within the cochlea and which is known to lead to the release of NO, was found to elicit similar electrophysiological and structural lesions in the cochlea. Pre-perfusion of scala tympani with L-methyl arginine (L-MA), which inhibits the release of NO, or superoxide dismutase (SOD), an O2-scavenger, conferred marked protection upon the cochlea from the lesions caused by NO donors. These observations indicate that enhanced NO production is likely to be an important factor responsible for pathological insult of the cochlea. The possibility is discussed that this factor is involved in the chain of events leading to hearing loss caused by bacterial meningitis. Such hearing loss is a major sequela of bacterial meningitis in children.
Subject(s)
Cochlea/physiology , Hearing Loss, Sensorineural/etiology , Meningitis, Bacterial/complications , Nitric Oxide/physiology , Action Potentials/drug effects , Animals , Cochlea/ultrastructure , Cochlear Microphonic Potentials/drug effects , Cochlear Microphonic Potentials/physiology , Enzyme Inhibitors/pharmacology , Guinea Pigs , Hearing Loss, Sensorineural/metabolism , Meningitis, Bacterial/metabolism , Microscopy, Electron, Scanning , N-Methylaspartate/pharmacology , Nitric Oxide/agonists , Nitric Oxide/antagonists & inhibitors , Nitroprusside/pharmacology , Penicillamine/analogs & derivatives , Penicillamine/pharmacology , S-Nitroso-N-Acetylpenicillamine , Scala Tympani/drug effects , Scala Tympani/ultrastructure , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitorsABSTRACT
Sensorineural hearing loss is a major sequela of the bacterial meningitis associated in particular with Streptococcus pneumoniae. Recent studies have shown pneumolysin, a toxin elaborated by S. pneumoniae, to be cytotoxic to the guinea pig cochlea. The mechanisms of this cytotoxicity are, however, not fully understood. In the present study this deleterious action of pneumolysin has been shown to be blocked by pretreating the cochlea with NG-methyl-L-arginine, a known inhibitor of nitric oxide synthesis. Furthermore, pretreatment of the cochlea with MK-801, an NMDA receptor antagonist, was also found to confer marked protection from the action of pneumolysin. This latter finding is consistent with previous reports that excess stimulation of NMDA receptors within the cochlea, an event known to lead to excess nitric oxide release, have similar effects on the cochlea as pneumolysin perfusion. It would therefore appear that nitric oxide may represent a significant link in the chain of events leading to the deafness of bacterial meningitis.