[Excitotoxic effect of glutamate on the afferent neurons in guinea pigs].

ABSTRACT

OBJECTIVE: To compare Glu-induced excitotoxic damage to the cochlear afferent neurons and changes of cochlear electrophysiology by directly injecting two different concentrations of glutamate into the inner ear of adult guinea pigs. METHODS: Guinea pigs were injected high doses glutamate (Glu-H,20 mmol/L, 10 microl) and low doses of glutamate (Glu-L, 10 mmol/L, 10 microl) into the perilymph of scala tympani. The compound action potential (CAP) was recorded and pathologic changes were evaluated with light and transmission electronic microscope at various time points after the application of glutamate. Results The thresholds of the CAP of Glu-L group (10 mmoL/L, less than one day) and Glu-H group (20 mmol/ L) were significantly increased compared with those of the normal group (P <0.001). But the thresholds of CAP of glutamate application (10 mmol/L, more than one week) weren't significantly different from those of the normal group (P > 0.05). Some changes of the spiral ganglion cells of the cochlear axis were observed in the 2 drug groups by light microscope. There were some vacuoles in the cell body and condensation of nuclear chromatin, shallow cellar liquid. The ratios of pathological changes between the control group and Glu-H group of different concentrations were notably different (P < 0.05). The observation under transmission electronic microscope found disvolution or necrosis of afferent nerve endings, myelinated nerve fibers, and model spiral ganglion cells. The pathological changes of the Glu-H group were more serious than those of the Glu-L group (10 mmol/L). The pathological changes of the Glu-L group would recover in 4 weeks, but those of the drug group would gradually deteriorate and degeneration would become necrosis. CONCLUSION: The morphologic changes and functional losses of afferent neurons in guinea pigs were caused by glutamate in scala tympani. The low dose (10 mmol/L) had induced reversible damage to cochlear afferent neurons. The high dose (20 mmol/L) had triggered irreversible neurodegeneration.