Sensorineural hearing loss from quinolinic acid: A neurotoxin in middle ear effusions

Abstract

Quinolinic acid (QUIN) is an endogenous metabolite that exerts a neurotoxic effect by binding to specific neuronal receptors. Studies involving a broad spectrum of infectious and inflammatory central nervous system diseases have suggested a role for QUIN in causing neuronal injury. Since there is evidence for presence of the QUIN receptor in mammalian cochleas, QUIN was measured in middle ear effusions (MEEs). Gas chromatography/mass spectrometry detected QUIN in each of 65 diluted human MEEs, with a mean of 482 +/- 75 (SEM) nmol/L and a range from 15 to 2667 nmol/L. QUIN was also detected in each of 197 chinchilla MEEs from five different models of otitis media, with a mean of 10.6 +/- 1.3 (SEM) mumol/L and a range from 0.23 to 146.0 mumol/L (corrected for dilution). To determine whether QUIN causes sensorineural hearing loss (SNHL), QUIN solutions were placed on round window membranes (RWM) for 20 to 240 minutes, in 20 chinchillas. SNHL was detected by electrocochleography in QUIN-exposed animals, but not in saline controls. We conclude that QUIN is present in MEEs and that QUIN in the middle ear has the potential to cross the RWM and cause sensorineural hearing loss, possibly by binding to specific neuronal receptors in mammalian cochleas.

Effects of hypoxia-inducible factor 1α on bone conduction impairment in otitis media with effusion

“…Yellon et al [6] found QUIN in the middle ear effusion, and confirmed the presence of QUIN in the murine otitis media models (at an average concentration of 10.6 ± 1.3 mmol/L). Moreover, they injected a QUIN solution into the middle ear cavities of mice for 1-4 h and observed the changes in the electrocochleography; their findings indicated that the severity of the sensorineural hearing loss correlated with the concentration of QUIN [6].…”

“…Yellon et al [6] found QUIN in the middle ear effusion, and confirmed the presence of QUIN in the murine otitis media models (at an average concentration of 10.6 ± 1.3 mmol/L). Moreover, they injected a QUIN solution into the middle ear cavities of mice for 1-4 h and observed the changes in the electrocochleography; their findings indicated that the severity of the sensorineural hearing loss correlated with the concentration of QUIN [6]. In the present study, although the levels of QUIN in the middle ear effusion seem to be higher in patients with bone conduction impairment than in patients without bone conduction impairment (4.33 ng/ml [1.00-144.80] vs 3.50 ng/ml [0-66.28]), no significant difference was found between the two groups, and no significant correlation between the levels of QUIN in the middle ear effusion and the BCT difference was observed.…”

“…One hypothesis suggests that certain noxious agents, for example several kinds of inflammatory mediators, might enter the inner ear through the round window membrane (RWM), resulting in inner ear damage [5]. Because of the semipermeability of the RWM, only those materials with small molecular weight (<1000 MW) can infiltrate easily [6]. Recent studies have shown that as small molecules, nitric oxide (NO, MW = 30) and quinolinic acid (QUIN, MW = 167) are present in the middle ear and can pass through the RWM into the inner ear; the presence of NO or QUIN in the inner ear may cause significant hearing loss [6,7].…”

“…Because of the semipermeability of the RWM, only those materials with small molecular weight (<1000 MW) can infiltrate easily [6]. Recent studies have shown that as small molecules, nitric oxide (NO, MW = 30) and quinolinic acid (QUIN, MW = 167) are present in the middle ear and can pass through the RWM into the inner ear; the presence of NO or QUIN in the inner ear may cause significant hearing loss [6,7]. As a free radical, NO may be directly responsible for significant cellular injury in the cochlea.…”

Fistula of the Cochlear Labyrinth in Noncholesteatomatous Chronic Otitis Media

“…Mechanical damage may include continuous trauma to the membranous labyrinth or a direct lesion of hair cells, leading to permanent fistulization between the endolymph and perilymph, causing a loss of inner ear potentials (23,24). Endogenous toxins that may be present in middle ear effusions (lipopolysaccharides, quinolinic acid, prostaglandins, and leukotrienes) are also possible mediators of sensorineural hearing loss (25)(26)(27)(28)(29)(30)(31). Endogenous toxins that may be present in middle ear effusions (lipopolysaccharides, quinolinic acid, prostaglandins, and leukotrienes) are also possible mediators of sensorineural hearing loss (25)(26)(27)(28)(29)(30)(31).…”