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Morphological changes in the vestibular epithelia and ganglion induced by ototoxic drug
K Sera1, Y Harada, N Tagashira
1Department of Otolaryngology, Hiroshima University School of Medicine, Japan.
Abstract:
The morphological changes of the vestibular sensory epithelia and the vestibular ganglions induced by Gentamicin(GM) were investigated using scanning electron microscope, transmission electron microscope and light microscope. The guinea pigs were injected with a single application of 4 mg (0.1ml) of GM into the middle ear through the tympanic membrane. The vestibular organs and the ganglions were observed up to 6 months after the treatment. Four days after the injection, fused, ballooned and missing cilia were observed in the vestibular sensory epithelia. These changes progressed and extended toward the periphery of the crista and the macula. The changes of the vestibular ganglions were first observed one month after the treatment. The degenerative process started from destruction of the mitochondrial cristae and vacuolization of the cytoplasm in the Schwann cell. The next step of the change was dissociation of the myelin sheath around the ganglion cell. The cytoplasmic organelles in the ganglion cell gradually deteriorated. At the later stage, the myelin sheath around the ganglion cell disappeared and the number of the cell reduced. Furthermore, the myelin sheath of the nerve fiber was dissociated. In this study the signs of the vestibular ganglion damage were later than that of the vestibular organ. However, we thought the changes in the ganglion are probably due to direct influence of GM, since the degeneration was found to develop in a relatively short period.
Insights
Gentamicin (GM) causes damage to vestibular sensory epithelia and vestibular ganglions in guinea pigs. Epithelial damage appears sooner than ganglion degeneration, though both result from direct GM influence.
Area of Science:
- Ototoxicity research
- Vestibular system science
- Neuroscience
Background:
- Gentamicin (GM) is an aminoglycoside antibiotic.
- Ototoxic effects of GM on the inner ear are well-documented.
- The precise mechanisms and temporal progression of GM-induced vestibular damage require further elucidation.
Purpose of the Study:
- To investigate the morphological changes in vestibular sensory epithelia and vestibular ganglions induced by Gentamicin (GM).
- To compare the onset and progression of damage in vestibular organs versus vestibular ganglions following GM exposure.
Main Methods:
- Guinea pigs were administered a single dose of GM (4 mg) into the middle ear.
- Morphological changes were assessed using scanning electron microscopy, transmission electron microscopy, and light microscopy.
- Observations were conducted over a 6-month period post-treatment.
Main Results:
- Within four days, vestibular sensory epithelia exhibited fused, ballooned, and missing cilia, progressing to cristae and maculae.
- Vestibular ganglion changes, including mitochondrial damage and myelin sheath dissociation, were observed one month post-treatment.
- Ganglion cell deterioration and reduced cell numbers were noted at later stages, with nerve fiber myelin sheath dissociation also occurring.
Conclusions:
- Vestibular organ damage manifests earlier than vestibular ganglion damage after GM administration.
- GM directly influences vestibular ganglion degeneration, as evidenced by the relatively rapid onset of observed changes.
- The study highlights the sequential and direct ototoxic effects of Gentamicin on the vestibular system.