Critical period for styrene ototoxicity in the rat.

The current experiments were undertaken to determine whether or not styrene-induced hearing loss in the rat depends more on the existence of a critical period between 14 and 21 weeks of age than on body weight. For these purposes, two experiments were carried out with mature Long-Evans rats. In the first experiment, two groups of 5-month old rats, but having different body weight (slim: 314 g vs. fat: 415 g) were exposed to 700 ppm styrene for 4 consecutive weeks, 5 days per week, 6 hours per day. In the second experiment, two groups of rats having the same weight: 345 g, but different ages (14- vs. 21- week old) were exposed to styrene in strictly identical experimental conditions. Auditory sensitivity was tested by recording evoked potentials from the inferior colliculus. Surface preparations of the organ of Corti were also performed to complete the investigation. At the end of the six week recovery period following the styrene exposure, a 7 dB permanent threshold shift (PTS) was obtained with the same age animals regardless of the body weight. Consequently, weight was not a major factor in styrene-induced hearing loss. Age was a more critical factor in determining higher sensitivity to styrene. Indeed, the three months old group had 23.5 dB PTS, whereas the five months old group had only a 7.7 dB PTS at 16 kHz. Thus, a 15 dB difference of PTS was obtained between the rats having the same weight but different age. While the weight does not play a major role in styrene ototoxicity, there is a critical period whose duration lasts more than three months and for which the susceptibility to styrene is enhanced.

Is the aged rat ear more susceptible to noise or styrene damage than the young ear?

Noise- and styrene-induced hearing and hair cell loss were studied in young (3 months) and aged (24-26 months) Long-Evans rats. The animals were exposed 6 h/d, 5 d/w for 4 weeks to (a) broadband noise centered at 8 kHz (92 or 97dB SPL), or b) styrene (700 ppm). Auditory sensitivity was tested by recording evoked potentials from the inferior colliculus. Histological analyses of the organ of Corti, stria vascularis, and the spiral ganglions were also performed. Aged controls showed outer hair cell (OHC) loss at the basal and apical regions of the organ of Corti, and an increase in pigmentation concomitant to a decrease in vascularization of the stria vascularis, along with elevated thresholds relative to young controls. The 92-dB noise caused similar threshold shifts in both age groups, whereas the 97-dB noise caused more threshold shifts in the aged group compared to the young group. Recovery of the hearing thresholds depended both on the intensity of the noise and on the age of the animals. Aged rats had minimal hair cell loss as a result of styrene exposure, whereas young animals showed significant OHC loss, particularly in third row. Despite significant loss of OHCs, the young subjects showed styrene-induced threshold shifts only at high frequencies. In summary, the data show that : (a) there is an influence of age on both noise-induced and styrene-induced threshold shift and hair cell loss in rats and (b) the cochlea appear to have a redundancy in the number of OHCs, thus threshold shift does not necessarily occur with significant OHC loss.