Noise
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- Category: Biophysical Research
- Last Updated on Tuesday, 11 December 2012 09:38
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At present it is hypothesized that NIHL is expressed with multiple effects on the inner ear. Besides the mechanical injury of the organ of Corti, due to the acoustical overstimulation, other subtle mechanisms involve the formation of reactive oxygen species -ROS- (Clerici et al, 1995; Jacono et al, 1998; Rao et al, 2001 ), the generation of nitric oxide and the co-involvement of glutamate receptors (Duan et al, 2000b) . Increased levels of ROS in the cochlea could cause cytotoxic effects through a variety of different biochemical mechanisms (Clerici et al, 1995; Ohinata et al, 2000a). The primary target of ROS is the mitochondria and the endoplasmatic reticulae. A number of in-vivo pilot studies has suggested that hair cell damage due to acoustic overstimulation can be effectively prevented by using drugs blocking the NMDA receptors , iron chelators and scavengers of reactive oxygen species (Agerman et al, 1999; Selvadurai et al, 2000; Soji et al; 2000a; 2000b; Shinohara et al, 2001; Suzuki et al, 2001). In vitro studies have also demonstrated that the administration of thiolic antioxidants increases the activity of respiratory mitochondrial enzymes, which in turn presumably attenuates the NIHL damage (Yamasoba et al, 1998).
In this context, current research indicates that an increase of the cellular level of antioxidants facilitates and enhances the oto-protective mechanisms of the inner ear. The cellular level of antioxidants in the inner ear can be increased by a number of pathways : 1) by gene-therapy which might generate the production of antioxidants (van de Water et al, 1999; Duan et al, 2000); (2) by introducing of a non-hydrolyzable adenosine analogue (R-PIA) which has been found effective in upregulating the antioxidant enzyme activity levels (Hu et al, 1997) ; 3) by administering a cysteine pro-drug, which promotes rapid restoration of glutathione -GSH- (Yamasoba et al, 1998 ) ; and 4) by administering antioxidants, such as neurotrophins and glutamate antagonists, by a local or a systemic infusion (Henderson et al, 1999 ). The round window is probably the most important soft tissue interface between the middle ear and inner ear that can be used for pharmacological therapy of inner ear disorders.
These otoprotection schemes target a high survival rate of outer hair cell (OHCs), inner hair cell(IHCs) and gaglion neurons. Testing the residual cochlear function (post-administration of the oto-protector) is commonly conducted with distortion product otoacoustic emissions spanning a wide range of frequencies i.e from 2.0 to 16.0 / 20.0 kHz (note: the reader should recall that the clinically employed TEOAEs, use click stimuli which in optimal conditions stimulate cochlear segments corresponding to 5-6 kHz). It is common to use Input-Output curves at a number of frequencies of interest (this depends on the animal species tested) and medium-intensity protocols ( i.e. 50-40 or 50-50 dB SPL) to evaluate the performance of the cochlear amplifier prior to saturation. The evaluation of the IHC and gaglion-neuron functional integrity is usually conducted with compound action potential (CAP) or ABR recordings. In theory functional alterations of the IHCs and the gaglion neurons are reflected by alterations to the efferent feedback effect on the OHCs, thus suppression studies might contribute information on the status of the auditory system "beyond" the OHCs.
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