Nitrogen and Oxygen Molecules in Meningitis-Associated Labyrinthitis and Hearing Impairment

Abstract

Pneumococcal meningitis remains a serious disease with a case fatality rate of 15%-25%. Furthermore, long-term residues affect up to 50% of survivors. One of the most frequent sequelae is sensorineural hearing loss, which occurs in 26% of survivors of pneumococcal meningitis. Unfortunately, sufficient treatment regimens are still missing. New insights into the pathology and pathophysiology of meningitis-associated hearing loss have come from animal models of bacterial meningitis. Most likely, bacteria reach the cochlea through the cochlear aquaeduct. Once arrived in the perilymphatic spaces, they induce a severe suppurative labyrinthitis. The blood-labyrinth barrier breaks, hair cells are damaged, and neurons in the spiral ganglion undergo cell death, leading to meningitis-associated hearing loss. Reactive oxygen and nitrogen species, in particular peroxynitrite, seem to be among the crucial mediators of cochlear damage and hearing loss during meningitis. In our rat model of pneumococcal meningitis, adjunctive therapy with the antioxidants and peroxynitrite scavengers Mn(III)tetrakis(4-bencoic acid)-porphyrin (MnTBAP) and N-Acetyl-L-Cystein (NAC) significantly attenuated acute and long-term hearing loss. In several other animal studies of pneumococcal meningitis, adjunctive antioxidant therapy also protected infected animals from intracranial complications. Therefore, the use of antioxidants seems to be a promising future treatment option in pneumococcal meningitis.

Adjunctive Daptomycin Attenuates Brain Damage and Hearing Loss More Efficiently than Rifampin in Infant Rat Pneumococcal Meningitis

“…Hearing loss during pneumococcal meningitis may result in part from the production of highly reactive oxygen species (ROS) (31). Treatment with rifampin has been shown to decrease the level of ROS compared to ceftriaxone in an experimental meningitis model in rabbits (9).…”

Pathogenesis and Pathophysiology of Pneumococcal Meningitis

“…Human observational studies have repeatedly found longterm sequelae after pneumococcal meningitis, including sensomotor deficit, hearing loss, and cognitive impairment, which may occur in up to 30% of surviving patients (202,241,496,497,500,526). Human histopathological data showed that the parenchymal damage was caused by increased ICP, cytotoxic and vasogenic edema, herniation, and local leukocyte infiltration or abscess formation, as well as by cortical necrosis and hippocampal neuronal loss (346,513).…”

“…Furthermore, TLR and MyD88 knockout mice demonstrated less hearing loss following pneumococcal meningitis (247). In a rat model, cochlear expression of iNOS and eNOS was upregulated following pneumococcal meningitis, and RNS-mediated cochlear damage could be attenuated both electrophysiologically and histopathologically by RNS scavengers (227,241,243). Earlier studies with guinea pigs showed that local perfusion of the scala tympani with NO donor compounds resulted in cochlear damage and could be attenuated by NO inhibitors or O 2 scavengers (14).…”

Otitis Related Disorders

“…Following entry of pathogens or irritants into the perilymphatic space contamination may progress into the membranous labyrinth and cause inflammation and damage to the cochlear and vestibular end organs. Oxidative stress triggered by the inflammatory process appears to be involved and may lead to cellular damage of hair cells and vestibular cochlear neurons (Abi-Hachem 2010; Klein et al, 2008).…”