Abstract
This study investigated the effect of systemic salicylate on central auditory and non-auditory structures in mice. Since cochlear hair cells are known to be one major target of salicylate, cochlear effects were reduced by using kanamycin to remove or impair hair cells. Neuronal brain activity was measured using the non-invasive manganese-enhanced magnetic resonance imaging technique. For all brain structures investigated, calcium-related neuronal activity was increased following systemic application of a sodium salicylate solution: probably due to neuronal hyperactivity. In addition, it was shown that the central effect of salicylate was not limited to the auditory system. A general alteration of calcium-related activity was indicated by an increase in manganese accumulation in the preoptic area of the anterior hypothalamus, as well as in the amygdala. The present data suggest that salicylate-induced activity changes in the auditory system differ from those shown in studies of noise trauma. Since salicylate action is reversible, central pharmacological effects of salicylate compared to those of (permanent) noise-induced hearing impairment and tinnitus might induce different pathophysiologies. These should therefore, be treated as different causes with the same symptoms.
Highlights
Salicylate is known to induce reversible loss of auditory sensitivity and tinnitus both in humans [1,2,3,4,5,6,7,8] and animals [9,10,11,12,13,14,15,16]
Hearing loss following kanamycin and bumetanide treatment was indicated by an auditory brainstem responses (ABR)-threshold shift of up to 40 dB in the investigated frequency range between 4 and 20 kHz compared to the untreated normal hearing control group
The results of the present study demonstrate changes in calcium-dependent brain activity after systemic salicylate application in kanamycin-treated animals using non-invasive manganeseenhanced magnetic resonance imaging (MEMRI)
Summary
Salicylate is known to induce reversible loss of auditory sensitivity and tinnitus both in humans [1,2,3,4,5,6,7,8] and animals [9,10,11,12,13,14,15,16]. The substance has been used in several animal studies that aimed to investigate the generation of tinnitus. Previous in-vivo and in-vitro studies have shown that acute application of sodium salicylate causes changes of outer (OHC) and inner (IHC) hair cell function, as well as an altered activity in central auditory and non-auditory structures. In the inner ear (the cochlea), salicylate leads to both functional and structural changes. Changes in IHC synaptic morphology occur [18] with hair cell resting potential modified
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