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Hearing loss caused by exposure to recreational and occupational noise remains a worldwide disabling condition and dysregulation of redox homeostasis is the hallmark of cochlear damage induced by noise exposure. In this review we discuss the dual function of ROS to both promote cell damage (oxidative stress) and cell adaptive responses (ROS signaling) in the cochlea undergoing a stressful condition such as noise exposure. We focus on animal models of noise-induced hearing loss (NIHL) and on the function of exogenous antioxidants to maintaining a physiological role of ROS signaling by distinguishing the effect of exogenous "direct" antioxidants (i.e. CoQ10, NAC), that react with ROS to decrease oxidative stress, from the exogenous "indirect" antioxidants (i.e. nutraceutics and phenolic compounds) that can activate cellular redox enzymes through the Keap1-Nrf2-ARE pathway. The anti-inflammatory properties of Nrf2 signaling are discussed in relation to the ROS/inflammation interplay in noise exposure. Unveiling the mechanisms of ROS regulating redox-associated signaling pathways is essential in providing relevant targets for innovative and effective therapeutic strategies against NIHL.

Background: Transcranial direct current stimulation (tDCS) is a non-invasive tool capable to modulate cortical functions by affecting neuronal excitability and synaptic plasticity. Objective: Here we investigated the effects of anodal tDCS on auditory cortex (ACx) in normal-hearing rats and following a paradigm of noise-induced hearing loss (NIHL), that causes morphological alterations in ACx pyramidal neurons. Methods: Male rats exposed to intense pure tone (10 kHz) were subsequently subjected to unilateral anodal tDCS of ACx and changes in dendritic morphology and spines were assessed by Golgi-Cox staining 30 days after the onset of the acoustic trauma. Molecular and functional changes were investigated by Western immunoblotting, immunofluorescence experiments and electrophysiological recordings in brain slices. Results: We found that NIHL altered dendritic morphology by decreasing spine density, mostly in layer 2/3 pyramidal neurons. Interestingly, tDCS increased ACx spine density, targeting apical dendrites of layer 2/3 and 5/6 pyramidal neurons in rats with normal auditory function and both apical and basal arborizations in layer 2/3 of NIHL rats. Twenty-four hours after tDCS, Bdnf and synaptophysin levels in ACx increased both in normal-hearing and noise-exposed rats. Field recordings showed that basal synaptic transmission at layer 2/3 horizontal connections was significantly reduced in noise-exposed rats compared to normal-hearing animals and, notably, input-output curves of noise-exposed animals subjected to tDCS were similar to those of normalhearing rats. Conclusions: Our findings provide novel evidence that anodal tDCS affects structural plasticity in the ACx suggesting that it might be beneficial in treating cortical alterations due to cochlear damage.

p66(shc), a member of the ShcA protein family, is essential for cellular response to oxidative stress, and elicits the formation of mitochondrial Reactive Oxygen Species (ROS), thus promoting vasomotor dysfunction and inflammation. Accordingly, mice lacking the p66 isoform display increased resistance to oxidative tissue damage and to cardiovascular disorders. Oxidative stress also contributes to noise-induced hearing loss (NIHL); we found that p66(shc) expression and serine phosphorylation were induced following noise exposure in the rat cochlea, together with markers of oxidative stress, inflammation and ischemia as indicated by the levels of the hypoxic inducible factor (HIF) and the vascular endothelial growth factor (VEGF) in the highly vascularised cochlear lateral region and spiral ganglion. Importantly, p66(shc) knock-out (p66 KO) 126 SvEv adult mice were less vulnerable to acoustic trauma with respect to wild type controls, as shown by preserved auditory function and by remarkably lower levels of oxidative stress and ischemia markers. Of note, decline of auditory function observed in 12 month old WT controls was markedly attenuated in p66KO mice consistent with delayed inner ear senescence. Collectively, we have identified a pivotal role for p66(shc) -induced vascular dysfunction in a common pathogenic cascade shared by noise-induced and age-related hearing loss.

Experimental and human investigations have raised the level of concern about the potential ototoxicity of organic solvents and their interaction with noise. The main objective of this study was to characterize the effects of the combined noise and styrene exposure on hearing focusing on the mechanism of damage on the sensorineural cells and supporting cells of the organ of Corti and neurons of the ganglion of Corti. The impact of single and combined exposures on hearing was evaluated by auditory functional testing and histological analyses of cochlear specimens. The mechanism of damage was studied by analyzing superoxide anion and lipid peroxidation expression and by computational analyses of immunofluorescence data to evaluate and compare the oxidative stress pattern in outer hair cells versus the supporting epithelial cells of the organ of Corti. The oxidative stress hypothesis was further analyzed by evaluating the protective effect of a Coenzyme Q10 analogue, the water soluble Qter, molecule known to have protective antioxidant properties against noise induced hearing loss and by the analysis of the expression of the endogenous defense enzymes. This study provides evidence of a reciprocal noise-styrene synergism based on a redox imbalance mechanism affecting, although with a different intensity of damage, the outer hair cell (OHC) sensory epithelium. Moreover, these two damaging agents address preferentially different cochlear targets: noise mainly the sensory epithelium, styrene the supporting epithelial cells. Namely, the increase pattern of lipid peroxidation in the organ of Corti matched the cell damage distribution, involving predominantly OHC layer in noise exposed cochleae and both OHC and Deiters’ cell layers in the styrene or combined exposed cochleae. The antioxidant treatment reduced the lipid peroxidation increase, potentiated the endogenous antioxidant defense system at OHC level in both exposures but it failed to ameliorate the oxidative imbalance

p66(shc), a member of the ShcA protein family, is essential for cellular response to oxidative stress, and elicits the formation of mitochondrial Reactive Oxygen Species (ROS), thus promoting vasomotor dysfunction and inflammation. Accordingly, mice lacking the p66 isoform display increased resistance to oxidative tissue damage and to cardiovascular disorders. Oxidative stress also contributes to noise-induced hearing loss (NIHL); we found that p66(shc) expression and serine phosphorylation were induced following noise exposure in the rat cochlea, together with markers of oxidative stress, inflammation and ischemia as indicated by the levels of the hypoxic inducible factor (HIF) and the vascular endothelial growth factor (VEGF) in the highly vascularised cochlear lateral region and spiral ganglion. Importantly, p66(shc) knock-out (p66 KO) 126 SvEv adult mice were less vulnerable to acoustic trauma with respect to wild type controls, as shown by preserved auditory function and by remarkably lower levels of oxidative stress and ischemia markers. Of note, decline of auditory function observed in 12 month old WT controls was markedly attenuated in p66KO mice consistent with delayed inner ear senescence. Collectively, we have identified a pivotal role for p66(shc) -induced vascular dysfunction in a common pathogenic cascade shared by noise-induced and age-related hearing loss.

In oncology, an emerging paradigm emphasises molecularly targeted approaches for cancer prevention and therapy and the use of adjuvant chemotherapeutics to overcome cisplatin limitations. Owing to their safe use, some polyphenols, such as curcumin, modulate important pathways or molecular targets in cancers. This paper focuses on curcumin as an adjuvant molecule to cisplatin by analysing its potential implications on the molecular targets, signal transducer and activator of transcription 3 (STAT3) and NF-E2 p45-related factor 2 (Nrf-2), in tumour progression and cisplatin resistance in vitro and the adverse effect ototoxicity in vivo.

Noise induced hearing loss depends on the progressive increase of reactive oxygen species and lipoperoxidative damage in conjunction with the imbalance of antioxidant defenses. The redox-sensitive transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in the regulation of cellular defense against oxidative stress including heme oxygenase-1 (HO-1) activation. In this work we describe a link between cochlear oxidative stress damage, induced by noise exposure, and the activation of Nrf2/HO-1 pathway. In our model, noise induces superoxide production and overexpression of the lipid peroxidation marker, 4-hydroxy-nonenals (4-HNE). To face the oxidative stress, the endogenous defense system is as well activated as shown by the slight activation of superoxide dismutases (SODs). In addition, we also observed the activation of the Nrf2/HO-1 pathway after noise exposure. In doing so, Nrf2 appears to promote the maintenance of cellular homeostasis under stress conditions. However, in this model the endogenous antioxidant system fails to counteract noise-induced cell damage and its activation is not enough effective in preventing the cochlear damage. The herb-derived phenol rosmarinic acid (RA) attenuates noise-induced hearing loss reducing threshold shift and promotes hair cell survival. In fact, RA enhances the endogenous antioxidant defenses as shown by the decreased superoxide production, the reduced expression of 4-HNE and the up-regulation of SODs. Interestingly, RA potentiates the Nrf2/OH-1 signaling pathway as shown by immunohistochemical and western blot analyses. Thus, protective effects of RA are associated with the induction/activation of Nrf2-ARE signaling pathway in addition to RA direct scavenging capability.

Growing evidence suggests that cochlear stressors as noise exposure and aging can induce homeostatic/maladaptive changes in the central auditory system from the brainstem to the cortex. Studies centered on such changes have revealed several mechanisms that operate in the context of sensory disruption after insult (noise trauma, drug-, or age-related injury). The oxidative stress is central to current theories of induced sensory-neural hearing loss and aging, and interventions to attenuate the hearing loss are based on antioxidant agent. The present review addresses the recent literature on the alterations in hair cells and spiral ganglion neurons due to noise-induced oxidative stress in the cochlea, as well on the impact of cochlear damage on the auditory cortex neurons. The emerging image emphasizes that noise-induced deafferentation and upward spread of cochlear damage is associated with the altered dendritic architecture of auditory pyramidal neurons. The cortical modifications may be reversed by treatment with antioxidants counteracting the cochlear redox imbalance. These findings open new therapeutic approaches to treat the functional consequences of the cortical reorganization following cochlear damage.

Noise exposure causes damage of multiple cochlear cell types producing permanent hearing loss with important social consequences. In mammals, no regeneration of either damaged hair cells or auditory neurons has been observed and no successful treatment is available to achieve a functional recovery. Loads of evidence indicate adipose-derived stem cells (ASCs) as promising tools in diversified regenerative medicine applications, due to the high degree of plasticity and trophic features. This study was aimed at identifying the path of in vivo cell migration and expression of trophic growth factors, upon ASCs transplantation into the cochlea, following noise-induced injury. ASCs were isolated in primary culture from the adipose tissue of a guinea pig, transduced using a viral vector to express the green fluorescent protein, and implanted into the scala tympani of deafened animals. Auditory function was assessed 3 and 7 days after surgery. The expression of trophic growth factors was comparatively analyzed using real-time PCR in control and noise-injured cochlear tissues. Immunofluorescence was used to assess the in vivo localization and expression of trophic growth factors in ASCs and cochleae, 3 and 7 days following homologous implantation. ASC implantation did not modify auditory function. ASCs migrated from the perilymphatic to the endolymphatic compartment, during the analyzed time course. Upon noise exposure, the expression of chemokine ligands and receptors related to the PDGF, VEGF, and TGFbeta pathways, increased in the cochlear tissues, possibly guiding in vivo cell migration. Immunofluorescence confirmed the increased expression, which appeared to be further strengthened by ASCs' implantation. These results indicated that ASCs are able to migrate at the site of tissue damage and express trophic factors, upon intracochlear implantation, providing an original proof of principle, which could pave the way for further developments of ASC-based treatments of deafnes

Short-term tinnitus develops shortly after the administration of a high dose of salicylate. Since salicylate selectively potentiates N-methyl- D-aspartate (NMDA) currents in spiral ganglion neurons, it may play a vital role in tinnitus by amplifying NMDA-mediated neurotransmission. The aim of this study was to determine whether systemic treatment with a NMDA channel blocker, memantine, could prevent salicylate-induced tinnitus in animals. Additional experiments were performed to evaluate the effect of memantine on the auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) to test for changes in hearing function. Thirty-six rats were divided into 3 groups and treated daily for four consecutive days. One group (n = 12) was injected with salicylate (300 mg/kg/d, IP), the second (n = 12) was treated with memantine (5 mg/kg/d, IP) and the third group (n = 12) was injected with salicylate and memantine. All rats were tested for tinnitus and hearing loss at 2, 24, 48 and 72 h after the first drug administration and 24 h post treatment; tinnituslike behaviour was assessed with gap prepulse inhibition of acoustic startle (GPIAS), and hearing function was measured with DPOAE, ABR and noise burst prepulse inhibition of acoustic startle (NBPIAS). Rats in the salicylate group showed impaired GPIAS indicative of transient tinnitus-like behaviour near 16 kHz that recovered 24 h after the last salicylate treatment. Memantine did not cause a significant change in GPIAS. Combined injection of salicylate and memantine significantly attenuated GPIAS tinnitus-like behaviour at 48 hours after the first injection. None of the treatments induced permanent threshold shifts in the ABR and DPOAE, which recovered completely within one day post treatment. Animals treated with salicylate plus memantine showed results comparable to animals treated with salicylate alone, confirming that there is no effect of memantine on DPOAE which reflects OHC function. The presen

Background Noise exposure impairs outer hair cells (OHCs). The common basis for OHC dysfunction and loss by acoustic over-stimulation is represented by reactive oxygen species (ROS) overload that may affect the membrane structural organization through generation of lipid peroxidation. Methods Here we investigated in OHC different functional zones the mechanisms linking metabolic functional state (NAD(P)H intracellular distribution) to the generation of lipid peroxides and to the physical state of membranes by two photon fluorescence microscopy. Results In OHCs of control animals, a more oxidized NAD(P)H redox state is associated to a less fluid plasma membrane structure. Acoustic trauma induces a topologically differentiated NAD(P)H oxidation in OHC rows, which is damped between 1 and 6 h. Peroxidation occurs after ~ 4 h from noise insult, while ROS are produced in the first 0.2 h and damage cells for a period of time after noise exposure has ended (~ 7.5 h) when a decrease of fluidity of OHC plasma membrane occurs. OHCs belonging to inner rows, characterized by a lower metabolic activity with respect to other rows, show less severe metabolic impairment. Conclusion and significance Our data indicate that plasma membrane fluidity is related to NAD(P)H redox state and lipid peroxidation which may represent key targets for therapeutic rescuing plan from noise insults.

To investigate whether curcumin may have in vivo protective effects against cisplatin ototoxicity by its direct scavenger activity and/or by curcumin-mediated upregulation of HO-1.

This study addresses the relationship between cochlear oxidative damage and auditory cortical injury in a rat model of repeated noise exposure. To test the effect of increased antioxidant defenses, a water-soluble coenzyme Q analog (Q) was used. We analyzed auditory function, cochlear oxidative stress, morphological alterations in auditory cortices and cochlear structures, and levels of coenzymes Q and Q (CoQ and CoQ, respectively) as indicators of endogenous antioxidant capability. We report three main results. First, hearing loss and damage in hair cells and spiral ganglion was determined by noise-induced oxidative stress. Second, the acoustic trauma altered dendritic morphology and decreased spine number of II-III and V-VI layer pyramidal neurons of auditory cortices. Third, the systemic administration of the water-soluble CoQ analog reduced oxidative-induced cochlear damage, hearing loss, and cortical dendritic injury. Furthermore, cochlear levels of CoQ and CoQ content increased. These findings indicate that antioxidant treatment restores auditory cortical neuronal morphology and hearing function by reducing the noise-induced redox imbalance in the cochlea and the deafferentation effects upstream the acoustic pathway.

Aminoglycosides, such as gentamycin, are well known ototoxic agents. Toxicity occurs via an activation process involving the formation of an iron-gentamycin complex with free radical production. Antioxidants like Q-ter (a soluble formulation of coenzyme Q(10), CoQ(10)), can limit or prevent cellular ototoxic damage. The present study was designed to investigate the possible protective effects of Q-ter on gentamycin ototoxicity in albino guinea pigs (250-300 g). Animals were divided into five experimental groups: I, a sham control group given an intra-peritoneal (I.P.) injection of 0.5 ml saline (SHAM); II, gentamycin group (GM), treated with an injection of gentamycin (100 mg/ kg); III, gentamycin + Q-ter group (GM+Q-ter), treated with gentamycin (same dose as group II) and an I.P. injection of coenzyme Q(10) terclatrate (Q-ter) at 100 mg/kg body weight; IV, injected with gentamycin (100 mg/kg) plus saline; V, treated with Q-ter alone (100 mg/ kg). All animals were treated for 14 consecutive days. Auditory function was evaluated by recording auditory brainstem responses (ABR) at 15 and 30 days from the beginning of treatment. Morphological changes were analyzed by rhodamine-phalloidine staining. Gentamycin-induced progressive high-frequency hearing loss of 45-55 dB SPL. Q-ter therapy slowed and attenuated the progression of hearing loss, yielding a threshold shift of 20 dB. The significant loss of outer hair cells (OHCs) in the cochlear medio-basal turn in gentamycin-treated animals was not observed in the cochleae of animals protected with Q-ter. This study supports the hypothesis that Q-ter interferes with gentamycin-induced free radical formation, and suggests that it may be useful in protecting OHC function from aminoglycoside ototoxicity, thus reducing hearing loss.

The effectiveness of a coenzyme Q10 formulation, Q-ter, given via transtympanic injection is interesting for the future application of this minimally invasive procedure in the treatment of reactive oxygen species (ROS)-induced hearing loss.

To identify a parameter to distinguish normal hearing from hearing impairment in the early stages. The parameter was obtained from transient-evoked otoacoustic emissions (TEOAEs), overcoming the limitations of the usually adopted waveform descriptive parameters which may fail in standard clinical screenings.

Conclusion: Our results are in agreement with the general idea that natural antioxidants achieve their best cytoprotective capacity if given before and soon after the stressor. Objective: We focused on ferulic acid (FA, 4-hydroxy 3-methoxycinnamic acid), a phenolic compound that is known to exhibit antioxidant properties. Our study was designed to evaluate the effectiveness of FA for different schedules of treatment to establish the 'therapeutic window' for FA protection. Methods: Guinea pigs were exposed to acoustic trauma (6 kHz at 120 dB for 60 min) and received a total dose of 600 mg/kg of FA. Group I, noise control; group II, noise + FA (150 mg/kg) for 4 days starting 24 h post exposure; group III, noise + FA (60 mg/kg) 1 h before and 9 days post exposure; group IV, noise + FA (60 mg/kg) given 3 days before and 7 days post exposure; group V, noise + FA (150 mg/kg) 1 h before and 3 days post noise exposure. Auditory brainstem response (ABR) test and immunohistochemical and morphological studies were performed. Results: Group V had significantly decreased noise-induced hearing loss at day 21 from noise exposure. The improvement of auditory function by FA was paralleled by a significant reduction in oxidative stress marker. The other schedules of drug administration showed a minor degree of protection

Presbycusis is the most common cause of hearing loss in aged subjects, reducing individual's communicative skills. Age related hearing loss can be defined as a progressive, bilateral, symmetrical hearing loss due to age related degeneration and it can be considered a multifactorial complex disorder, with both environmental and genetic factors contributing to the aetiology of the disease. The decline in hearing sensitivity caused by ageing is related to the damage at different levels of the auditory system (central and peripheral). Histologically, the aged cochlea shows degeneration of the stria vascularis, the sensorineural epithelium, and neurons of the central auditory pathways. The mechanisms responsible for age-associated hearing loss are still incompletely characterized. This work aims to give a broad overview of the scientific findings related to presbycusis, focusing mainly on experimental studies in animal models

Our results are in agreement with the general idea that natural antioxidants achieve their best cytoprotective capacity if given before and soon after the stressor.

Presbycusis is the most common cause of hearing loss in aged subjects, reducing individual's communicative skills. Age related hearing loss can be defined as a progressive, bilateral, symmetrical hearing loss due to age related degeneration and it can be considered a multifactorial complex disorder, with both environmental and genetic factors contributing to the aetiology of the disease. The decline in hearing sensitivity caused by ageing is related to the damage at different levels of the auditory system (central and peripheral). Histologically, the aged cochlea shows degeneration of the stria vascularis, the sensorineural epithelium, and neurons of the central auditory pathways. The mechanisms responsible for age-associated hearing loss are still incompletely characterized. This work aims to give a broad overview of the scientific findings related to presbycusis, focusing mainly on experimental studies in animal models.

Using an excised pig heart preparation with tubes, a manometer, and a visualizing apparatus, Giulio Ceradini, an Italian physiologist working in the years of 1871–1872 in Carl Ludwig’s famous laboratory in Leipzig, Germany, illustrated the mechanism of closure of the semilunar valves. He was the first to conceive that the closure of the heart valves depends not on a static back pressure nor upon eddies but is primarily the consequence of the decelerated systolic efflux. This pioneer research of Ceradini was first published in German in 1872 (4). The purpose of the present report is to revisit Ceradini’s pioneering experiments and his interpretation of heart valve closure, which remains as true as it was in 1872.

This study analysed the acoustic and vestibular functional and morphological modifications in guinea pigs after acoustic trauma. Animals were exposed to noise (6 kHz, at 120 dB SPL for 60 minutes) and then auditory brainstem responses (ABR) and vestibulo-ocular reflex (VOR) were measured at 6 hours, 1 day, 3, 7, and 21 days after noise. Western blotting and immunostaining for 4-hydroxy-2-noneal (4-HNE) and vascular endothelial growth factor (VEGF) were performed in the cochlear and vestibular regions at 1 and 7 days after noise exposure. A significant decrease of VOR gain was observed on day 1 and the recovery was completed at day 21. ABR threshold values reached a level of 80 dB at day 1 after trauma reaching a value of about 50 dB SPL on day 21. 4-HNE expression, a marker of lipid peroxidation was strongly increased in the cochlea. In the vestibule, 4-HNE immunoreactivity was faint. However, VEGF was up-regulated both in the cochlea and vestibule. In conclusion, the expression of VEGF in both cochlear and vestibular structures suggests a reparative role with potentially therapeutic implications.

The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS) also in noise induced hearing loss (NIHL) and anti-oxidants and free-radicals scavengers have been shown to attenuate the damage. Coenzyme Q(10) (CoQ(10)) or ubiquinone has a bioenergetic role as a component of the mithocondrial respiratory chain, it inhibits mitochondrial lipid peroxidation, inducing ATP production and it is involved in ROS removal and prevention of oxidative stress-induced apoptosis. However the therapeutic application of CoQ(10) is limited by the lack of solubility and poor bio- availability, therefore it is a challenge to improve its water solubility in order to ameliorate the efficacy in tissues and fluids. This study was conducted in a model of acoustic trauma in the guinea pig where the effectiveness of CoQ(10) was compared with a soluble formulation of CoQ(10) (multicomposite CoQ(10) Terclatrate, Q-ter) given intraperitoneally 1 h before and once daily for 3 days after pure tone noise exposure (6 kHz for 1 h at 120 dB SPL). Functional and morphological studies were carried out by measuring auditory brainstem responses, scanning electron microscopy for hair cell loss count, active caspase 3 staining and terminal deoxynucleotidyl trasferase-mediated dUTP labelling assay in order to identify initial signs of apoptosis. Treatments decreased active caspase 3 expression and the number of apoptotic cells, but animals injected with Q-ter showed a greater degree of activity in preventing apoptosis and thus in improving hearing. These data confirm that solubility of Coenzyme Q(10) improves the ability of CoQ(10) in preventing oxidative injuries that result from mitochondrial dysfunction. (C) 2008 Elsevier B.V. All rights reserved.

Increasing evidence suggests the involvement of oxidative stress in noise-induced hearing loss. The present study analysed, in an animal experimental model, the time course of the pathogenic mechanisms of noise-induced cochlear damage and the efficacy of the antioxidant drug N-acetylcysteine in reducing noise ototoxicity. Animals were divided into two groups, exposed to noise one treated with N-acetylcysteine for 3 days and one (the control group) with saline. Acoustic trauma was induced by a continuous pure tone of 6 kHz, at 120 dB SPL for 30 minutes. Electrocochleographic recordings were made from an implanted round window electrode and the compound action potentials were measured daily at 2-16 kHz for 7 days. Morphological changes were analysed by scanning electron microscopy. The acoustic threshold measured 1 hour after acoustic trauma was elevated in the control group to 70-90 dB in the higher frequencies of the compound action potential audiogram, with a maximum threshold elevation ranging between 12 and 16 kHz. During the first 24 h, following acoustic trauma, there was a partial recovery of compound action potential thresholds of about 20 dB to reach a final threshold elevation of about 50-70 dB; there was no further improvement over the remaining experimental week. Animals treated with N-acetylcysteine showed a similar temporary threshold shift but a clear improvement in the recovery of compound action potential thresholds, with significantly reduced permanent threshold shift and hair cell loss. These data suggest that N-acetylcysteine is able to attenuate the toxic effect of acoustic trauma and could represent an interesting molecule for preventing inner ear injuries.

This study analysed the acoustic and vestibular functional and morphological modifications in guinea pigs after acoustic trauma. Animals were exposed to noise (6 kHz, at 120 dB SPL for 60 minutes) and then auditory brainstem responses (ABR) and vestibulo-ocular reflex (VOR) were measured at 6 hours, 1 day, 3, 7, and 21 days after noise. Western blotting and immunostaining for 4-hydroxy-2-noneal (4-HNE) and vascular endothelial growth factor (VEGF) were performed in the cochlear and vestibular regions at 1 and 7 days after noise exposure. A significant decrease of VOR gain was observed on day 1 and the recovery was completed at day 21. ABR threshold values reached a level of 80 dB at day 1 after trauma reaching a value of about 50 dB SPL on day 21. 4-HNE expression, a marker of lipid peroxidation was strongly increased in the cochlea. In the vestibule, 4-HNE immunoreactivity was faint. However, VEGF was up-regulated both in the cochlea and vestibule. In conclusion, the expression of VEGF in both cochlear and vestibular structures suggests a reparative role with potentially therapeutic implications.

Idebenone, a synthetic analogue of coenzyme Q, attenuates noise-induced hearing loss by virtue of its antioxidant properties. This study involves a guinea pig model of acoustic trauma where the effectiveness of idebenone is analyzed in comparison with Vitamin E (alpha-tocopherol) that exhibits a potent antioxidant activity in the inner ear. Idebenone and vitamin E were injected intraperitoneally 1 h before noise exposure and once daily for three days; functional and morphological studies were then carried out, respectively, by auditory brainstem responses evaluation, scanning electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay identification of missing and apoptotic cells was also performed. The results showed that the protective effects of idebenone and vitamin E were not additive implying that the two antioxidants may share competitive mechanisms.

Nella pratica stereoelettroencefalografica (SEEG) uno dei mezzi più efficaci per la identificazione della zona epilettogena si riassume nella ricerca della sede di origine dell'attività epilettica critica.