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Adrien A Eshraghi

Publications and source records attributed to Adrien A Eshraghi.

At least 19 recordsLinked to original sources
PubMed2006

Blocking c-Jun-N-terminal kinase signaling can prevent hearing loss induced by both electrode insertion trauma and neomycin ototoxicity.

Neomycin ototoxicity and electrode insertion trauma both involve activation of the mitogen activated protein kinase (MAPK)/c-Jun-N-terminal kinase (JNK) cell death signal cascade. This article discusses mechanisms of cell death on a cell biology level (e.g. necrosis and apoptosis) and proposes the blocking of JNK signaling as a therapeutic approach for preventing the development of a permanent hearing loss that can be initiated by either neomycin ototoxicity or electrode insertion trauma. Blocking of JNK molecules incorporates the use of a peptide inhibitor (i.e. D-JNKI-1), which is specific for all three isoforms of JNK and has been demonstrated to prevent loss of hearing following either electrode insertion trauma or loss of both hearing and hair cells following exposure to an ototoxic level of neomycin. We present previously unpublished results that control for the effect of perfusate washout of aminoglycoside antibiotic by perfusion of the scala tympani with an inactive form of D-JNKI-1 peptide, i.e. JNKI-1(mut) peptide, which was not presented in the original J. Neurosci. article that tested locally delivered D-JNKI-1 peptide against both noise- and neomycin-induced hearing loss (i.e. Wang, J., Van De Water, T.R., Bonny, C., de Ribaupierre, F., Puel, J.L., Zine, A. 2003a. A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss. J. Neurosci. 23, 8596-8607). D-JNKI-1 is a cell permeable peptide that blocks JNK signaling at the level of the three JNK molecular isoforms, which when blocked prevents the increases in hearing thresholds and the loss of auditory hair cells. This unique therapeutic approach may have clinical application for preventing: (1) hearing loss caused by neomycin ototoxicity; and (2) the progressive component of electrode insertion trauma-induced hearing loss.

Animals↗
PubMed2006

Cochlear implantation trauma and noise-induced hearing loss: Apoptosis and therapeutic strategies.

Cochlear implantation trauma and noise-induced hearing loss both involve a physical disruption of the organ of Corti and may involve several mechanisms of cell death at the molecular level, i.e., necrosis, necrosis-like programmed cell death (PCD; type 2 PCD), and apoptosis (type 1 PCD). This article reviews several promising therapeutic strategies that are currently being developed. One of these promising new strategies involves the use of a highly effective peptide inhibitor of the c-Jun N-terminal kinase cell death signal cascade (i.e., D-JNKI-1) to prevent apoptosis of injured auditory hair cells. Our recent studies showed prevention of cochlear implantation-induced hearing loss by infusing this peptide into the cochlea of guinea pigs. Another otoprotective therapy under investigation is the application of mild hypothermia to protect the cochlea from the development of a hearing loss that follows exposure to a physical trauma, e.g., electrode array insertional trauma. These forward-looking strategies have the potential of improving hearing outcomes after cochlear implantation and providing novel means of otoprotection from noise-induced trauma.

Animals↗
PubMed2006

Glutathione ester protects against hydroxynonenal-induced loss of auditory hair cells.

OBJECTIVE: Test the ability of glutathione monoethyl ester (GSH(e)) to protect auditory hair cells against the ototoxic effects of 4-hydroxy-2,3-nonenal (HNE). STUDY DESIGN AND SETTING: Organ of Corti explants were either untreated or treated with one of a series of four concentrations of GSH(e) for one day, then exposed to HNE. Counts of FITC-phalloidin-labeled hair cells determined both HNE ototoxicity and GSH(e) otoprotection. RESULTS: HNE was toxic to hair cells at physiologically relevant levels, eg, 400 muM, and GSH(e) provided a significant level of protection against HNE ototoxicity (P < 0.05) at all levels tested, ie, 1.16 to 9.3 mM. CONCLUSION: GSH(e) protects auditory hair cells from damage and loss initiated by a naturally occurring ototoxic molecule, ie, HNE (a by-product of oxidative stress). SIGNIFICANCE: Treatment with GSH(e) may be an effective therapy to protect the cochlea against the adverse effects of traumas (eg, electrode insertion) that generate oxidative stress.

Aldehydes↗
PubMed2006

Triamcinolone acetonide protects auditory hair cells from 4-hydroxy-2,3-nonenal (HNE) ototoxicity in vitro.

CONCLUSION: Triamcinolone acetonide crystalline suspension (e.g. Volon A) was not ototoxic to the auditory hair cells present within organ of Corti explants and protected them from an ototoxic molecule, i.e. 4-hydroxy-2,3-nonenal (HNE), that is produced within the organ of Corti as a result of oxidative stress-induced damage. OBJECTIVES: To test the corticosteroid, triamcinolone acetonide, for ototoxicity and otoprotective capacity in organ of Corti explants. MATERIALS AND METHODS: Organ of Corti explants excised from 4-day-old rats were the test system, HNE was the ototoxin challenge. Hair cell integrity counts were performed with fluorescent microscopy on fixed explants stained with FITC-labeled phalloidin. Statistical significance was set at p<0.05. RESULTS: Triamcinolone acetonide did not affect hair cell integrity in the organ of Corti explants and it provided a high level of protection of hair cells against the ototoxic effects of a damaging level of HNE as determined by hair cell density counts.

Aldehydes↗
PubMed2006

D-JNKI-1 treatment prevents the progression of hearing loss in a model of cochlear implantation trauma.

HYPOTHESES: 1) Hearing loss caused by electrode insertion trauma has both acute and delayed components; and 2) the delayed component of trauma-initiated hearing loss can be prevented by a direct delivery of a peptide inhibitor of the c-Jun N-terminal kinase cell death signal cascade, that is, D-JNKI-1, immediately after the electrode insertion within the cochlea. BACKGROUND: Acute trauma to the macroscopic elements of the cochlea from electrode insertion is well known. The impact of trauma-induced oxidative stress within injured cochlear tissues and the efficacy of drugs (e.g., D-JNKI-1) to prevent apoptosis of damaged hair cells is not well defined. METHODS: Hearing function was tested by pure-tone evoked auditory brainstem responses (ABRs) and distortion products of otoacoustic emissions (DPOAEs). D-JNKI-1 in artificial perilymph (AP) or AP alone was delivered into the scala tympani immediately after electrode trauma and for 7 days. Controls were nontreated contralateral and D-JNKI-1-treated ears without electrode insertion trauma. RESULTS: There was no increase in the hearing thresholds of either the contralateral control ears or in the D-JNKI-1 without trauma animals. There was a progressive increase in ABR thresholds and decrease in DPOAE amplitudes after electrode insertion trauma in untreated and in AP-treated cochleae. Treatment with D-JNKI-1 prevented the progressive increase in ABR thresholds and decrease in DPOAE amplitudes that occur after electrode insertion trauma. CONCLUSION: Hearing loss caused by cochlear implant electrode insertion trauma in guinea pigs has both acute and delayed components. The delayed component can be prevented by treating the cochlea with D-JNKI-1.

Analysis of Variance↗
PubMed2006

Vibrant soundbridge surgery: evaluation of transcanal surgical approaches.

UNLABELLED: Since its introduction, surgery for the placement of the Vibrant Soundbridge (VSB) device has been performed using a facial recess approach. Because of the size of the VSB device, this approach requires a large facial recess that can lead to complications, i.e., facial palsy and/or taste disturbance. The purpose of this study is to develop and compare transcanal surgical approaches for leading the VSB into the middle ear. SETTING: Cadaver temporal bones in a university temporal bone laboratory. MATERIALS AND METHODS: First, two experienced senior surgeons validated the three possible approaches in human temporal bone: 1) the classical facial recess approach; 2) a small mastoidectomy, elevation of a tympanomeatal flap, small atticotomy, 0.5-mm cutting of the bony external auditory canal (EAC) from the cortical plane on its approximately two-thirds to three-fourths and then a trough to pass the electrode array into the middle ear; and 3) similar to the second approach but with replacing the cutting of the bony EAC with a tunnel from the mastoid cavity to the EAC. Both the second and third approaches were transcanal. Next, five residents and six attending surgeons performed the three operations and evaluate these different approaches by using analog visual scales (VAS) for each procedure. They assess the following: 1) the ease of passing the electrode array and the Floating Mass Transducer (FMT) into the middle ear, 2) the ease for FMT clipping, and 3) their self-confidence using each approach. Time required for the three operations was measured. Measurements of landmarks were obtained on all temporal bones. Two patient cases illustrate the clinical application of this new surgical approach. RESULTS: The two transcanal approaches were assessed to be easier, faster, and safer methods for VSB surgery than the classic facial recess approach. CONCLUSION: VSB surgery has been performed using a facial recess approach with risk for facial nerve and taste disturbance. Transcanal approaches are good alternative for this surgery. Three major limitations are to be assessed in future patient studies: the pathologic findings of the EAC, the design of the FMT regarding the axis of the ossicular chain, the long-term evaluation of the skin of the external ear canal.

Aged↗
PubMed2006

Conservation of residual acoustic hearing after cochlear implantation.

OBJECTIVE: This study was designed to test the hypothesis that partial hearing conservation is attainable after cochlear implantation with a long perimodiolar electrode. Surgical strategies for hearing conservation during cochlear implantation are described. STUDY DESIGN: Prospective, single-subject, repeated-measures design. SETTING: Academic tertiary care center. PATIENTS: Twenty-eight severely to profoundly hearing-impaired adult cochlear implant recipients who had some measurable hearing preoperatively. INTERVENTION: Cochlear implantation using Nucleus Freedom Contour Advance electrode. MAIN OUTCOME MEASURES: Preimplant and postimplant pure-tone thresholds and speech recognition scores were obtained to determine the incidence and degree of conserved hearing at a mean interval of 9 (+/-3.9) months. RESULTS: Thirty-two percent of subjects experienced complete conservation of hearing (0- to 10-dB loss), and 57% experienced partial conservation of hearing (>11 dB) after implantation. However, open-set speech recognition was partially conserved in only one subject. Cochlear implant performance was not better in patients with conservation of residual hearing. CONCLUSION: Conservation of pure-tone hearing was possible in 89% of implanted patients; however, residual speech perception was not conserved with this long perimodiolar electrode. A ceiling effect tends to inflate the prevalence of hearing conservation in implantation studies of severely to profoundly hearing-impaired patients.

Adult↗
PubMed2006

Prevention of cochlear implant electrode damage.

PURPOSE OF REVIEW: As the current trend in cochlear implantation is to prescribe cochlear implants for patients with residual hearing and to use electroacoustic stimulation, cochlear implant damage must be prevented. This article summarizes current research endeavors to prevent electrode insertion trauma and resulting hearing loss. RECENT FINDINGS: Alteration in surgical technique is necessary with each new electrode design. Nontraumatic surgical technique also requires minimizing acoustic trauma due to drilling the cochleostomy, mechanical damage from electrode insertion, potential infection, and fibrosis of the cochlea. The pattern of hearing loss following electrode insertion trauma is an immediate loss that results from direct trauma to the macroscopic elements of the cochlea and a delayed loss that may reflect the activation of inflammatory and cell death pathways. Therapies under investigation include glucocorticoids, inhibitors of cell death pathways, and hypothermia. SUMMARY: Electrode insertion trauma-induced hearing loss involves multiple mechanisms ranging from mechanical insertion trauma to activation of inflammatory and cell death pathways. The macroscopic mechanical damage to the cochlea may be prevented by improvement of electrode design and surgical technique. The molecular damage needs further studies to assess the efficacy of novel therapeutic strategies in preserving functional residual hearing.

Animals↗
PubMed2005

Cochlear temperature correlates with both temporalis muscle and rectal temperatures. Application for testing the otoprotective effect of hypothermia.

CONCLUSIONS: During systemic hypothermia, the internal temperature of the rat cochlea correlates best with the temporalis muscle and rectal temperatures. These positive correlations will be used in future studies to assess the efficacy of mild and moderate hypothermia to protect hearing against the progressive loss caused by electrode insertion in a clinically relevant model of cochlear implantation trauma. OBJECTIVE: To monitor the internal temperature of the cochlea during induced systemic hypothermia using a reference tissue instead of an internal cochlear temperature probe. MATERIAL AND METHODS: The temperatures of the cochlea, brain, temporalis muscle and rectum were determined during periods of normothermia (37 degrees C), mild (33 degrees C) and moderate (30 degrees C) hypothermia and slow rewarming in anesthetized adult Fisher rats. These values were compared using statistical analysis to establish the best correlations between the temperature of the cochlea and the temperature at the three other temperature measurement sites. RESULTS: The strongest correlations with the internal temperature of the cochlea during the induction of mild-to-moderate hypothermia were obtained for the temperatures of the ipsilateral temporalis muscle and rectum.

Animals↗
PubMed2005

Pattern of hearing loss in a rat model of cochlear implantation trauma.

HYPOTHESIS: Trauma caused by cochlear implant electrode insertion is attributable to the combination of direct physical trauma and the delayed cell death of oxidative stress-injured auditory sensory cells. BACKGROUND: Histologic evaluation of cochlear implant electrode trauma has demonstrated that the extent of sensory cell losses is proportional to the degree of injury. However, the impact of delayed oxidative stress within injured cochlear tissues and the progressive loss of injured hair cells by way of apoptosis are at present unknown. METHODS: Laboratory rats were evaluated for hearing acuity before and after electrode insertion, before and after round window membrane incision only. Hearing was measured before trauma or incision and over the next 7 days. Objective measurements of hearing function were distortion products of otoacoustic emissions (DPOAEs) in the frequency range of 2 to 32 kHz and tone-burst (i.e., 4-32 kHz) evoked auditory brain stem responses (ABRs). RESULTS: For the experimental cochleae, there were progressive increases in ABR thresholds and decreases in ABR amplitudes. The amplitude of the DPOAEs in the experimental cochleae also showed progressive decreases. For the contralateral control and round window membrane surgical control ears, there were no significant changes in either DPOAE or ABR thresholds. CONCLUSION: These results document a progressive loss of hearing acuity postimplantation and strongly suggest that electrode insertion trauma generated oxidative stress within injured cochlear tissues.

Animals↗
PubMed2005

Mild hypothermia protects auditory function during cochlear implant surgery.

OBJECTIVE/HYPOTHESIS: Loss of auditory function after cochlear implant (CI) electrode insertion occurs in two stages in the laboratory rat. An immediate loss is followed by a progressive loss over 7 days. Similar stages of acute and progressive neuronal loss occur after trauma in the central nervous system where hypothermia has been shown to have a protective effect. We hypothesize that hypothermia has a similar protective effect against loss of auditory function caused by CI electrode insertion trauma. METHODS: Thirty rats underwent surgery in one cochlea; the contralateral ear was an unoperated control. In the normothermia group, CI electrode insertion trauma was generated with rectal temperature maintained at 37 degrees C throughout the experiment. In the mild hypothermia group, electrode trauma was generated with rectal temperature lowered to 34 degrees C. In the surgical control group, mock surgery was performed at 37 degrees C. Multiple frequency auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) testing of all ears was performed before surgery, immediately afterward, and on postoperative days 3, 5, and 7. RESULTS: Both ABR and DPOAE testing demonstrated partial loss of auditory function after electrode insertion trauma. However, the hypothermia group had significantly less functional loss in the immediate stage and no significant loss in the progressive stage. CONCLUSION: Mild hypothermia protects auditory function during CI electrode insertion.

Animals↗
PubMed2004

Evaluation of hearing and auditory nerve function by combining ABR, DPOAE and eABR tests into a single recording session.

In this article, we describe an efficient method for testing both auditory receptor and auditory nerve function in a single recording session. Auditory receptor function is tested in response to pure tone, tone burst and click acoustic stimuli (i.e. distortion products of otoacoustic emissions, DPOAE; and auditory-evoked brainstem responses, ABR). The function of the auditory neurons and nerve is measured in response to direct electric current stimulation (i.e. electrically evoked auditory brainstem responses, eABR). All measurements were obtained from anesthetized laboratory rats during single recording sessions using hardware and software stimulation and analysis programs developed by Intelligent Hearing Systems, Miami, FL.

Acoustic Stimulation↗
PubMed2004

Changes in programming over time in postmeningitis cochlear implant users.

OBJECTIVE: Although successful cochlear implantation of patients with deafness following meningitis is expected, long-term stability of electrical current requirements has not been systematically evaluated. This study evaluated changes in programming for patients deafened by bacterial meningitis and stability of auditory performance over time. STUDY DESIGN AND SETTING: In this retrospective descriptive study, cochlear implant (CI) stimulation mode and performance of 14 patients deafened by meningitis were compared with those of an age-matched control group of patients deafened by other causes. RESULTS: There were no significant differences in mean performance between the meningitis group and control group (P > 0.05). However, the postmeningitis group required progressively higher stimulation levels and higher programming modes over time as compared to the control group. CONCLUSIONS: Even with deafness accompanied by labyrinthine ossification attributed to meningitis, neural elements were present and could be stimulated. Because increasing levels of stimulation were required over time, postmeningitic children with CIs, and those with cochlear ossification in particular, may need frequent programming adjustments to maintain performance. SIGNIFICANCE: These patients need close follow-up of stimulation levels and programming modes postoperatively in order to perform optimally with CIs. EBM RATING: B-3.

Adolescent↗
PubMed2003

Comparative study of cochlear damage with three perimodiolar electrode designs.

OBJECTIVE: To describe intracochlear insertion trauma caused by three perimodiolar cochlear implant electrodes. STUDY DESIGN: Descriptive histological study of 15 human cadaver temporal bones. METHODS: Fifteen cadaver temporal bones underwent surface preparation and were implanted with one of the following perimodiolar electrode arrays: Combi 40+PM (MedEl Corporation), HiFocus II (Advanced Bionics Corporation), or Contour (Cochlear Corporation). A cryosectioning technique was used to study horizontal sections at 200 microm intervals with the electrode in place. Image-enhanced videofluoroscopy and computer-assisted morphometrics were used to assess the mechanism of insertion trauma and to determine electrode position within the modiolus. RESULTS: Histological examination revealed varying degrees of damage to the spiral ligament, basilar membrane, and osseous spiral lamina. Using a novel grading system for electrode trauma, there was no statistically significant difference among the three electrodes. A literature search of histological studies of a commonly used "standard" electrode showed damage equal to or greater than that seen in the current study. CONCLUSIONS: Insertion trauma caused by periomodiolar electrodes occurs to an acceptable degree. Refinement of electrodes based on mechanisms of trauma may be able to further reduce damage.

Basilar Membrane↗
PubMed2003

Arrest of apoptosis in auditory neurons: implications for sensorineural preservation in cochlear implantation.

HYPOTHESIS: The JNK/c-Jun cell death pathway is a major pathway responsible for the loss of oxidative stress-damaged auditory neurons. BACKGROUND: Implantation of patients with residual hearing accentuates the need to preserve functioning sensorineural elements. Although some auditory function may survive electrode insertion, the probability of initiating an ongoing loss of auditory neurons and hair cells is unknown. Cochlear implantation can potentially generate oxidative stress, which can initiate the cell death of both auditory neurons and hair cells. METHODS: Dissociated cell cultures of P4 rat auditory neurons identified the apoptotic pathway initiated by oxidative stress insults (e.g., loss of trophic factor support) and characterized this pathway by arresting translation of pathway-specific mRNA with antisense oligonucleotide treatment and with the use of pathway specific inhibitors. The presence or absence of apoptosis-specific protein and changes in the level of neuronal survival measured the efficacy of these interventional strategies. RESULTS: These in vitro studies identified the JNK/c-Jun cascade as a major initiator of apoptosis of auditory neurons in response to oxidative stress. Neurons pretreated with c-jun antisense oligonucleotide and exposed to high levels of oxidative stress were rescued from apoptosis, whereas neurons in treatment control cultures died. Treatment of oxidative-stressed cultures with either curcumin, a MAPKKK pathway inhibitor, or PD-098059, a MEK1 inhibitor, blocked loss of neurons via the JNK/c-Jun apoptotic pathway. CONCLUSION: Blocking the JNK/c-Jun cell death pathway is a feasible approach to treating oxidative stress-induced apoptosis within the cochlea and may have application as an otoprotective strategy during cochlear implantation.

Animals↗