dizocilpine-maleate and Hearing-Loss--Sensorineural

Our study investigated the neurotoxicity of quinolinic acid (QA) to spiral ganglion cells (SGCs), observed the protective effects of N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and magnesium ions on the QA-induced injury to SGCs, and analyzed the role of QA in otitis media with effusion (OME)-induced sensorineural hearing loss (SNHL). After culture in vitro for 72 h, SGCs were exposed to different media and divided into 4 groups: the blank control group, the QA injury group, the MK-801 treatment group, and the MgCl2 protection group. The apoptosis rate of SGCs was analyzed by Annexin V and PI double staining under the fluorescence microscopy 24 h later. SGCs were cultured in vitro for 72 h and divided into four groups: the low concentration QA group, the high concentration QA group, the MK-801 group, the MgCl2 group. The transient changes of intracellular calcium concentration were observed by the laser scanning confocal microscopy. Apoptosis rate in QA injury group was higher than that in blank control group and MgCl2 protection group (both P<0.05), but there was no significant difference between MK-801 treatment group and blank control group (P>0.05). In high concentration QA group, there was an obvious increase of the intracellular calcium concentration in SGCs, which didn't present in low concentration QA group. In MgCl2 group, the peak values of the intracellular calcium concentration in SGCs were reduced and the duration was shortened, but the intracellular calcium concentration in SGCs had no significant change in MK-801 group. It was concluded that QA could injure SGCs by excessively activating NMDA receptors on the cell membrane, which might be the mechanism by which OME induced SNHL, while Mg2+ could protect the SCGs from the neurotoxicity of QA.

Topics: Animals; Animals, Newborn; Apoptosis; Calcium; Cells, Cultured; Dizocilpine Maleate; Hearing Loss, Sensorineural; Magnesium Chloride; Otitis Media with Effusion; Quinolinic Acid; Rats; Receptors, N-Methyl-D-Aspartate; Spiral Ganglion

Exotoxin A, produced by Pseudomonas aeruginosa (PaExoA), penetrates from the middle ear in to the cochlea and causes sensorineural hearing loss (SNHL). In this investigation we studied electrophysiological changes in the albino rat following instillation of PaExoA and N(G)-nitro-L-arginine methyl ester (L-NAME), a known inhibitor of nitric oxide synthesis, into the middle ear. Hearing thresholds were measured by auditory brainstem response (ABR) technique. Latency/intensity curves were constructed to distinguish between cochlear and conductive components of hearing loss. PaExoA caused damage to cochleae and SNHL, mainly at high frequencies. This impairment was blocked by (L-NAME). It would appear that nitric oxide may be a significant link in the mechanism of SNHL caused by bacterial toxin. L-NAME acts as an otoprotectant against the deleterious action of PaExoA.

Topics: Animals; Auditory Threshold; Cochlea; Dizocilpine Maleate; Enzyme Inhibitors; Evoked Potentials, Auditory, Brain Stem; Exotoxins; Hearing Loss, Conductive; Hearing Loss, High-Frequency; Hearing Loss, Sensorineural; NG-Nitroarginine Methyl Ester; Nitric Oxide; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Severity of Illness Index

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Dizocilpine Maleate; Guinea Pigs; Hair Cells, Auditory, Outer; Hearing Loss, Sensorineural; Humans; Neuroprotective Agents; Piperidines; Risk Factors