Useful Noise Damaged FX MULTiFORMAT

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Pamula Harrison

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Jul 11, 2024, 12:58:38 PM7/11/24
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As mentioned above, both salicylate-induced and noise-induced tinnitus can be blocked in animals by local (cochlear) application of NMDA antagonists (Guitton et al., 2003; Guitton and Dudai, 2007). Local application allows the use of very small doses of pharmacological agent, without major side effects in the brain. The time window of sensitivity to NMDA antagonists is several days after the trauma itself, which provides a long enough time to act to cure tinnitus. However, local organ-targeted molecular pharmacology approaches could still be used after these first several days following the insult. Indeed, as NMDA receptors seem to be common molecular integrators at the first stages of tinnitus, other molecular pathways could be involved in the later plastic changes underlying tinnitus. The molecular pathways critically involved in pathophysiological mechanisms of auditory structures represent appealing candidates for pharmacological targets to cure long-term tinnitus. Among them, cytoskeletal plasticity, with proteins such as Microtubule-associated Proteins (MAPs) or activity-dependent cytoskeletal protein (Arg3.1, also known as Arc) represents an interesting molecular pathway to investigate (Ladrech et al., 2004; Panford-Walsh et al., 2008). MAP has been reported to play a key-role in several pathophysiological conditions in the cochlea, ranging from synaptic reorganization following noise overexposure in the cochlea (Ladrech et al., 2004), to reaction to aminoglycoside toxicity (Ladrech and Lenoir, 2002). Expression of several MAP isoforms (in particular the MAP2c isorform, known for its role during the development of neurons) appears to be tightly regulated during the repair processes that occur in primary auditory neurons after excitotoxic injury in the cochlea, as well as after cochlear intoxication by amikacin, one of the well-known ototoxic drug (Ladrech and Lenoir, 2002; Ladrech et al., 2004). In this last case, the MAP pathway has been suggested to play a key role in the survival of the remaining damaged sensory cells (Ladrech and Lenoir, 2002). Results obtained on animal models of salicylate-induced tinnitus demonstrated change of Arg3.1 and BDNF during salicylate treatment in auditory structures, reinforcing the interest of cytoskeleton proteins as potential targets of research for tinnitus (Panford-Walsh et al., 2008; Singer et al., 2008). An alternative way to look at this problem of dysfunction of cochlear plasticity in tinnitus is to modulate the GABA-dependant inhibition in the cochlea. Recent works demonstrated that intra-cochlear application of midazolam [a GABA(A) receptor modulator] resulted in the reversion of salicylate-induced perception in animals (Panford-Walsh et al., 2008).

Useful Noise Damaged FX MULTiFORMAT


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