Salicylate Induces Tinnitus through Activation of Cochlear NMDA Receptors

Guitton, Matthieu J.; Caston, J.; Ruel, Jérôme; Johnson, Randolph M.; Pujol, Rémy; Puel, Jean–Luc

doi:10.1523/jneurosci.23-09-03944.2003

Cited by 288 publications

(306 citation statements)

References 49 publications

Supporting

Mentioning

283

Contrasting

Unclassified

Order By: Relevance

“…It is one of the most common solvents for dissolving hydrophobic compounds employed in vivo or in vitro studies. DMSO has frequently been used in studies of the inner ear; however, its potential side effects are unknown and have been largely overlooked in previous studies (Basile et al, 1996;Guitton et al, 2003;Harris et al, 2005;Lee et al, 2002;So et al, 2005). Our in vitro results obtained with postnatal cochlear cultures showed little or no evidence of hair cell damage following 24 h treatment with 0.25% DMSO or less.…”

Section: Discussionmentioning

confidence: 54%

Cytotoxic effects of dimethyl sulphoxide (DMSO) on cochlear organotypic cultures

2008

View full text Add to dashboard Cite

The amphipathic molecule dimethyl sulphoxide (DMSO) is a solvent often used to dissolve compounds applied to the inner ear; however, little is known about its potential cytotoxic side effects. To address this question, we applied 0.1 to 6% DMSO for 24 h to cochlear organotypic cultures from postnatal day 3 rats and examined its cytotoxic effects. DMSO concentrations of 0.1% and 0.25% caused little or no damage. However, concentrations between 0.5 and 6% resulted in stereocilia damage, hair cell swelling and a dose-dependent loss of hair cells. Hair cell damage began in the basal turn of the cochlea and spread towards the apex with increasing concentration. Surprisingly, DMSO-induced damage was greater for inner hair cells than outer hair cell whereas nearby supporting cells were largely unaffected. Most hair cell death was associated with nuclear shrinkage and fragmentation, morphological features consistent with apoptosis. DMSO treatment induced TUNEL positive staining in many hair cells and activated both initiator caspase-9 and caspase-8 and executioner caspase-3; this suggests that apoptosis is initiated by both intrinsic mitochondrial and extrinsic membrane cell death signaling pathways.

show abstract

Section: Discussionmentioning

confidence: 54%

Cytotoxic effects of dimethyl sulphoxide (DMSO) on cochlear organotypic cultures

2008

View full text Add to dashboard Cite

show abstract

“…Experiments were performed on 78 adult female rats (body weight, 180 -250 g). Pharmacological agents were applied to the inner ear as described previously by Guitton et al (2003). Surgery was performed under general anesthesia induced with isoflurane (Baxter S.A., Lessignes, Belgium), using a Minerve apparatus (induction of 10 min at 2.5%, maintenance at 2% under 0.8 L of O 2 /min).…”

Section: Methodsmentioning

confidence: 99%

Control of Hair Cell Excitability by Vestibular Primary Sensory Neurons

et al. 2007

View full text Add to dashboard Cite

In the rat utricle, synaptic contacts between hair cells and the nerve fibers arising from the vestibular primary neurons form during the first week after birth. During that period, the sodium-based excitability that characterizes neonate utricle sensory cells is switched off. To investigate whether the establishment of synaptic contacts was responsible for the modulation of the hair cell excitability, we used an organotypic culture of rat utricle in which the setting of synapses was prevented. Under this condition, the voltage-gated sodium current and the underlying action potentials persisted in a large proportion of nonafferented hair cells. We then studied whether impairment of nerve terminals in the utricle of adult rats may also affect hair cell excitability. We induced selective and transient damages of afferent terminals using glutamate excitotoxicity in vivo. The efficiency of the excitotoxic injury was attested by selective swellings of the terminals and underlying altered vestibular behavior. Under this condition, the sodium-based excitability transiently recovered in hair cells. These results indicate that the modulation of hair cell excitability depends on the state of the afferent terminals. In adult utricle hair cells, this property may be essential to set the conditions required for restoration of the sensory network after damage. This is achieved via re-expression of a biological process that occurs during synaptogenesis.

show abstract

“…Methods in the animal laboratory include gap pre-pulse inhibition of acoustic startle (Yang et al, 2007), schedule-induced polidypsia avoidance conditioning (Lobarinas et al, 2004;Yang et al, 2007), active avoidance (Guitton et al, 2003) and conditioned suppression and avoidance (Jastreboff and Sasaki, 1994). While some conditioning paradigms can provide estimates of pitch and loudness (Jastreboff and Sasaki, 1994), a complete characterisation of the perceptual and psychological attributes of TI cannot be established in laboratory animals.…”

Section: Guiding Principles From Animal Studiesmentioning

confidence: 99%

The mechanisms of tinnitus: Perspectives from human functional neuroimaging

2009

View full text Add to dashboard Cite

In this review, we highlight the contribution of advances in human neuroimaging to the current understanding of central mechanisms underpinning tinnitus and explain how interpretations of neuroimaging data have been guided by animal models. The primary motivation for studying the neural subtrates of tinnitus in humans has been to demonstrate objectively its representation in the central auditory system and to develop a better understanding of its diverse pathophysiology and of the functional interplay between sensory, cognitive and affective systems. The ultimate goal of neuroimaging is to identify subtypes of tinnitus in order to better inform treatment strategies. The three neural mechanisms considered in this review may provide a basis for TI classification. While human neuroimaging evidence strongly implicates the central auditory system and emotional centres in TI, evidence for the precise contribution from the three mechanisms is unclear because the data are somewhat inconsistent. We consider a number of methodological issues limiting the field of human neuroimaging and recommend approaches to overcome potential inconsistency in results arising from poorly matched participants, lack of appropriate controls and low statistical power. AbstractIn this review, we highlight the contribution of advances in human neuroimaging to the current understanding of central mechanisms underpinning tinnitus and explain how interpretations of neuroimaging data have been guided by animal models. The primary motivation for studying the neural subtrates of tinnitus in humans has been to demonstrate objectively its representation in the central auditory system and to develop a better understanding of its diverse pathophysiology and of the functional interplay between sensory, cognitive and affective systems. The ultimate goal of neuroimaging is to identify subtypes of tinnitus in order to better inform treatment strategies. The three neural mechanisms considered in this review may provide a basis for TI classification. While human neuroimaging evidence strongly implicates the central auditory system and emotional centres in TI, evidence for the precise contribution from the three mechanisms is unclear because the data are somewhat inconsistent. We consider a number of methodological issues limiting the field of human neuroimaging and recommend approaches to overcome potential inconsistency in results arising from poorly matched participants, lack of appropriate controls and low statistical power.

show abstract

Salicylate Induces Tinnitus through Activation of Cochlear NMDA Receptors

Cited by 288 publications

References 49 publications

Cytotoxic effects of dimethyl sulphoxide (DMSO) on cochlear organotypic cultures

Cytotoxic effects of dimethyl sulphoxide (DMSO) on cochlear organotypic cultures

Control of Hair Cell Excitability by Vestibular Primary Sensory Neurons

The mechanisms of tinnitus: Perspectives from human functional neuroimaging

Contact Info

Product

Resources

About