Trauma-specific insults to the cochlear nucleus in the rat.

The effect of acoustic overstimulation on the neuronal number of the cochlear nucleus (CN) was investigated by using unbiased stereological methods in rats. We found that, after 9 weeks of recovery, neurons in the anteroventral cochlear nucleus (AVCN) degenerated, whereas those in the posteroventral and dorsal cochlear nuclei (PVCN and DCN) were preserved. The noise trauma induced near complete loss of the outer hair cells throughout the cochlea, and the inner hair cells were preserved only in the more apical regions. This pattern of selective loss of AVCN neurons in this study was different from trauma induced by auditory deafferentation by mechanical compression of auditory neurons. In contrast to noise trauma, mechanical compression caused loss of neurons in the PVCN and DCN. After 5 weeks of recovery from mechanical compression, there was no loss of inner or outer hair cells. These findings indicate that auditory deprivation, induced by different experimental manipulations, can have strikingly different consequences for the central auditory system. We hypothesized that AVCN neuronal death was induced by excitotoxic mechanisms via AMPA-type glutamate receptors and that excitatory neuronal circuits developed after acoustic overstimulation protected the PVCN and DCN against neuronal death. The results of the present study demonstrate that hearing loss from different etiologies will cause different patterns of neuronal degeneration in the CN. These findings are important for enhancing the performance of cochlear implants and auditory brainstem implants, because diverse types of hearing loss can selectively affect neuronal degeneration of the CN.

Selective vulnerability of adult cochlear nucleus neurons to de-afferentation by mechanical compression.

It is well established that the cochlear nucleus (CN) of developing species is susceptible to loss of synaptic connections from the auditory periphery. Less information is known about how de-afferentation affects the adult auditory system. We investigated the effects of de-afferentation to the adult CN by mechanical compression. This experimental model is quantifiable and highly reproducible. Five weeks after mechanical compression to the axons of the auditory neurons, the total number of neurons in the CN was evaluated using un-biased stereological methods. A region-specific degeneration of neurons in the dorsal cochlear nucleus (DCN) and posteroventral cochlear nucleus (PVCN) by 50% was found. Degeneration of neurons in the anteroventral cochlear nucleus (AVCN) was not found. An imbalance between excitatory and inhibitory synaptic transmission after de-afferentation may have played a crucial role in the development of neuronal cell demise in the CN. The occurrence of a region-specific loss of adult CN neurons illustrates the importance of evaluating all regions of the CN to investigate the effects of de-afferentation. Thus, this experimental model may be promising to obtain not only the basic knowledge on auditory nerve/CN degeneration but also the information relevant to the application of cochlear or auditory brainstem implants.

Effects of a single high dose of cisplatin on the melanocytes of the stria vascularis in the guinea pig.

The antineoplastic drug cisplatin is known to cause a reduction in endocochlear potential. The hypothesis to be tested was whether a single high dose of cisplatin affects the melanocytes by altering the expression of melanin. Pigmented guinea pigs received a bolus injection of cisplatin (8 mg/kg as a 15-second intravenous infusion). Auditory brainstem response (ABR) thresholds and morphological analysis of the hair cells and the stria vascularis were made 96 h after injection. ABR thresholds were elevated (15-40 dB) at 12-30 kHz and a significant loss of outer hair cells in the more basal regions was found. Cisplatin caused a significantly lower density of melanin in the intermediate cells in the basal region without any signs of apoptosis. Changes in melanin content were not noted in the middle or apical cochlear regions. Significant correlations were found between melanin density, ABR threshold shifts and outer hair cell loss in the region corresponding to 30 kHz. The findings reported here further support the multiple cytotoxic effect of cisplatin on the inner ear.

The guide to plotting a cochleogram.

The cochleogram is commonly used for illustrating hair cell loss after insult, yet standardized procedures for plotting either individual or averaged cochleograms are lacking despite more than 40 years of use. Due to the intra-species variation in basilar membrane (BM) length, it is important that length is plotted on the cochleogram in percent and not millimeter. It is also of interest to correlate the location of lesion to frequency by using a frequency-place equation. However, there is no consensus as which equation is most suitable for the species under study. This is an important issue since two different equations can result in significantly different frequency-place maps for the same cochlea. The purpose of this presentation is to suggest procedures for standardizing the cochleogram. The guidelines include: (i) basilar membrane length should be plotted as percent instead of millimeter due to the biological variation that exists in BM length within a particular species and strain, and the total length in millimeter stated on the cochleogram; (ii) the equations used for frequency-place maps should be stated on the cochleogram; (iii) different basilar membrane lengths should be normalized to percent before averaged cochleograms are made. These procedures are illustrated and discussed.

Auditory peripheral influences on calcium binding protein immunoreactivity in the cochlear nucleus during aging in the C57BL/6J mouse.

The C57BL/6J (C57) mouse was selected as a suitable model for early presbyacusis to determine if there were correlations between peripheral pathology (spiral ganglion loss, inner and outer hair cell loss) and calcium binding immunoreactivity in the cochlear nucleus during aging. The quantitative stereological method, the optical fractionator, was used for determining the total number of neurons and calcium binding immunopositive neurons (calbindin, parvalbumin and calretinin) during aging in the posteroventral- and dorsal cochlear nucleus (PVCN and DCN) in C57 mice. Comparing 30-month-old to 1-month-old C57 mice, a percent increase in parvalbumin and calbindin immunoreactivity was evident in both the PVCN and DCN. Correlations were made between peripheral pathology (spiral ganglion and inner and outer hair cell loss) and calcium binding protein expression. Significant correlations between cochlear pathology and the percentage of parvalbumin and calretinin immunoreactive neurons were demonstrated in the DCN. Moreover, significant correlations were found between cochlear pathology and parvalbumin and calbindin in the PVCN. In summary, the findings imply that degenerative changes in the auditory periphery can modulate neuronal homeostasis by increasing calcium binding proteins in the PVCN and DCN during aging. Taken together, these findings suggest a role for calcium binding proteins in protecting against age-induced calcium toxicity.

Extra inner hair cells in the developing rabbit cochlea.

Development of the rabbit inner ear was analysed with respect to the presence of extra inner hair cells (XIHCs) in phalloidin-impregnated cochleas of newborn rabbits 0, 3 and 5 days of age. The number of XIHCs ranged from four to 77. The distribution was asymmetrical with a peak in the apical 3 mm of the cochlea. There was no general disorganisation in the vicinity of the XIHCs, and the numbers were highly symmetrical between the two ears. The number was significantly larger (P<0.001) in newborns than in adults. There was no correlation between number of XIHCs and cochlear length, making it unlikely that the presence of XIHCs is due to lack of space in the ordinary row of IHCs. The possible relation of the XIHCs to growth factors, molecular genetics and regeneration is discussed.