Noise-induced Hearing Loss In Rats Research Articles

Targeted therapeutic hypothermia protects against noise induced hearing loss.

Exposure to occupational or recreational loud noise activates multiple biological regulatory circuits and damages the cochlea, causing permanent changes in hearing sensitivity. Currently, no effective clinical therapy is available for the treatment or mitigation of noise-induced hearing loss (NIHL). Here, we describe an application of localized and non-invasive therapeutic hypothermia and targeted temperature management of the inner ear to prevent NIHL. We developed a custom-designed cooling neck collar to reduce the temperature of the inner ear by 3-4°C post-injury to deliver mild therapeutic hypothermia. This localized and non-invasive therapeutic hypothermia successfully mitigated NIHL in rats. Our results show that mild hypothermia can be applied quickly and safely to the inner ear following noise exposure. We show that localized hypothermia after NIHL preserves residual hearing and rescues noise-induced synaptopathy over a period of months. This study establishes a minimally-invasive therapeutic paradigm with a high potential for rapid translation to the clinic for long-term preservation of hearing health.

Hydralazine alleviates noise-induced hearing loss by scavenging acrolein

Noise-induced hearing loss (NIHL) is the most common cause of hearing loss. This study investigates the therapeutic efficacy of the acrolein scavenger hydralazine for NIHL in rats. NIHL was induced by exposure to a continuous pure tone of 10 kHz. Auditory function was evaluated by auditory brainstem response (ABR) testing and scanning electron microscopy. The expression of acrolein and glial cell markers GFAP and OX42 was assessed by immunofluorescence staining. The protein and mRNA expression of GFAP, OX42, interleukin-18 (IL-18), IL-1β, and fractalkine (FTK) was measured by qRT-PCR and western blotting. A rat model of NIHL was successfully developed, as evidenced by increased ABR thresholds. The results showed that noise exposure increased the expression of acrolein, GFAP, OX42, FTK, IL-1β, and IL-18 in the rat cochlear nucleus. Furthermore, hydralazine alleviates NIHL by reversing the effects of acrolein. These results demonstrate that acrolein is involved in glial cell activation and NIHL, it’s also a therapeutic potential target for NIHL.

The potential therapeutic and/or protective effects of steroid, PRP and melatonin on noise-induced hearing loss in rats

The potential therapeutic and/or protective effects of steroid, PRP and melatonin on noise-induced hearing loss in rats

Superoxide dismutase@zeolite Imidazolate Framework-8 Attenuates Noise-Induced Hearing Loss in Rats.

Reactive oxygen species (ROS) and inflammation have been considered major contributors to noise-induced hearing loss (NIHL) that constituted a public health threat worldwide. Nanoantioxidants, with high antioxidant activity and good stability, have been extensively used in the study of ROS-related diseases. In this study, we constructed a superoxide dismutase (SOD)@zeolite imidazolate framework-8 (ZIF-8) nanoparticle based on biomimetic mineralization and applied it to a rat model of NIHL. Our results showed that SOD@ZIF-8 effectively protected the animals from hearing loss and hair cell loss caused by noise. ROS, oxidative damage, and inflammation of noise-damaged cochlea were attenuated considerably after SOD@ZIF-8 administration. Importantly, we found that SOD@ZIF-8 achieved nanotherapy for NIHL in rats via a primary effect on the Sirtuin-3 (SIRT3)/superoxide dismutase2 (SOD2) signaling pathway without obvious adverse side effects. Therefore, our study is expected to open up a new field for NIHL treatment, and lay a foundation for the application of nanomaterials in other ROS-related inner ear diseases.

Effect of Electroacupuncture on Noise-Induced Hearing Loss in Rats.

Acupuncture has long been used to relieve some inner ear diseases such as deafness and tinnitus. The present study examined the effect of electroacupuncture (EA) on noise-induced hearing loss (NIHL) in animals. A NIHL rat model was established. Electroacupuncture pretreatment at 2 Hz or posttreatment at the right Zhongzhu (TE3) acupoint was applied for 1 hour. Auditory thresholds were measured using auditory brainstem responses (ABRs), and histopathology of the cochlea was examined. The results indicated that the baseline auditory threshold of ABR was not significantly different between the control (no noise), EA-only (only EA without noise), noise (noise exposure only), pre-EA (pretreating EA then noise), and post-EA (noise exposure then posttreating with EA) groups. Significant auditory threshold shifts were found in the noise, pre-EA, and post-EA groups in the immediate period after noise exposure, whereas auditory recovery was better in the pre-EA and post-EA groups than that in the noise group at the three days, one week (W1), two weeks (W2), three weeks (W3), and four weeks(W4) after noise stimulation. Histopathological examination revealed greater loss of the density of spiral ganglion neurons in the noise group than in the control group at W1 and W2. Although significant loss of spiral ganglion loss happened in pre-EA and post-EA groups, such loss was less than the loss of the noise group, especially W1. These results indicate that either pretreatment or posttreatment with EA may facilitate auditory recovery after NIHL. The detailed mechanism through which EA alleviates NIHL requires further study.

Combination photobiomodulation/N-acetyl-L-cysteine treatment appears to mitigate hair cell loss associated with noise-induced hearing loss in rats.

Sensorineural hearing loss is an intractable disease. Acoustic overstimulation creates hearing loss; many patients exhibit social and emotional dysfunctions. In a model of noise-induced hearing loss (NIHL), low-level laser photobiomodulation (PBM) at a near-infrared wavelength significantly improved auditory brainstem response (ABR) thresholds. In addition, both N-acetyl-L-cysteine (NAC) and acetyl-L-carnitine (ALCAR) attenuated NIHL, reducing the effects of noise trauma in the cochlea and the central auditory system. Here, we combined PBM with antioxidants to explore hearing threshold recovery and morphological hair cell changes after rats were exposed to noise. The average auditory brainstem response thresholds after PBM/NAC combination treatment were reduced from the apex to the basal turn at all of 8, 16, and 32 kHz compared to the noise-only group. The PBM/NAC combination treated group exhibited intact outer hair cells in all turns, and significantly greater hair cell numbers in the middle and basal cochlear turns, than did controls. Thus, PBM/NAC treatment may prevent hearing dysfunction caused by NIHL.

Oral Antioxidant Vitamins and Magnesium Limit Noise-Induced Hearing Loss by Promoting Sensory Hair Cell Survival: Role of Antioxidant Enzymes and Apoptosis Genes.

Noise induces oxidative stress in the cochlea followed by sensory cell death and hearing loss. The proof of principle that injections of antioxidant vitamins and Mg2+ prevent noise-induced hearing loss (NIHL) has been established. However, effectiveness of oral administration remains controversial and otoprotection mechanisms are unclear. Using auditory evoked potentials, quantitative PCR, and immunocytochemistry, we explored effects of oral administration of vitamins A, C, E, and Mg2+ (ACEMg) on auditory function and sensory cell survival following NIHL in rats. Oral ACEMg reduced auditory thresholds shifts after NIHL. Improved auditory function correlated with increased survival of sensory outer hair cells. In parallel, oral ACEMg modulated the expression timeline of antioxidant enzymes in the cochlea after NIHL. There was increased expression of glutathione peroxidase-1 and catalase at 1 and 10 days, respectively. Also, pro-apoptotic caspase-3 and Bax levels were diminished in ACEMg-treated rats, at 10 and 30 days, respectively, following noise overstimulation, whereas, at day 10 after noise exposure, the levels of anti-apoptotic Bcl-2, were significantly increased. Therefore, oral ACEMg improves auditory function by limiting sensory hair cell death in the auditory receptor following NIHL. Regulation of the expression of antioxidant enzymes and apoptosis-related proteins in cochlear structures is involved in such an otoprotective mechanism.

The protective effect of metformin against the noise-induced hearing loss.

To test the protective effect of metformin against noise-induced hearing loss. 24 rats were included in the study. The first group was exposed to noise only, the second group took metformin, the third group was exposed to noise and took metformin, and the fourth group was neither exposed to noise nor took metformin as control group. After measurement of baseline DPOAE and ABR of rats, the metformin group and the metformin + noise group received 300mg/kg/day metformin via gavage for 10days. On the 11th day, group 1 and group 3 were exposured to white noise at 105dB SPL for 15h. After noise exposure, DPOAE and ABR measurements of all rats were repeated on days 1st, 7th, and 21st. At the end of the study, all animals were sacrificed and cochlear tissues were separated for immunohistochemical assessments. ABR threshold values and DPAOE measurements of groups 1 and 3 were deteriorated on the 1st day after noise, while deterioration in group 1 continued on 7th and 21st days, but normalized on 7th day in group 3. After immune staining, a significant immunoreaction was observed in the noise group, while the reaction in the noise + metformin group was close to the control group. Metformin has a protective effect on noise-induced hearing loss in rats. As a conclusion, it is determined that metformin protects from permanent threshold shift in rats. It can be considered a good alternative for protecting noise-induced hearing loss.

The Effects of Normobaric Hyperoxia Pre- and Post-treatment on the Development of Noise-Induced Hearing Loss in Rats

Background: Occupational noise exposure is one of the leading factors for developing noise-induced hearing loss (NIHL), particularly among workers worldwide. The literature review reveals that beside conventional strategies for preventing NIHL, multiple interventions can be applied to reduce or prevent such disorders. The present study aimed to investigate the preventive effects of normobaric hyperoxia pre- and post-treatment on the development of NIHL in rats. Methods: Four groups of male Wistar rats were exposed to pure oxygen alone, noise alone, or oxygen plus noise for 6 hours a day, 5 days a week for 4 weeks. One group served as the control and received neither noise nor oxygen. Animals in the noise groups were exposed to high-pass white noise of 100 dB SPL, centred at 8 KHz. The treatment protocols were based on inhalation of pure normobaric oxygen (95%) for 3 hours in a chamber either before or after noise exposure. The auditory brainstem responses (ABRs) for click and 4, 6, 8, 12, and 16 kHz stimuli, as well as distortion product otoacoustic emissions (DPOAEs) at 4, 6, 8, and 10 kHz, were recorded to assess the level of hearing impairment before exposure and 4 weeks post-exposure. Results: The results showed that pre-treatment of rats with 3 hours of normobaric hyperoxia contributed to a significant reduction in ABR threshold shifts, while improving the DPOAE amplitudes (P 0.05). Conclusions: Pre- and post-treatment with normobaric hyperoxia seem to produce protective effects through either boosting cellular oxygenation or maximizing antioxidant enzyme activities and tolerance against noise-induced ischemia and hypoxia in the cochlea. Therefore, application of normobaric hyperoxia pre- or post-treatment, along with other conventional protective strategies, can be helpful in the fight against NIHL.

Minocycline attenuates noise-induced hearing loss in rats

Noise-induced hearing loss (NIHL) is a serious health concern and prevention of hair cell death or therapeutic intervention at the early stage of NIHL is critical to preserve hearing. Minocycline is a semi-synthetic derivative of tetracycline and has been shown to have otoprotective effects in ototoxic drug-induced hearing impairment, however, whether minocycline can protect against NIHL has not been investigated. The present study demonstrated elevated ABR (auditory brainstem response) thresholds and outer hair cell loss following traumatic noise exposure, which was mitigated by intraperitoneal administration of minocycline (45mg/kg/d) for 5 consecutive days. In conclusion, the present study demonstrated that minocycline, a clinically approved drug with a good safety profile, can attenuate NIHL in rats and may potentially be used for treatment of hearing loss in clinic.

Olfactory epithelium neural stem cell implantation restores noise-induced hearing loss in rats

ObjectiveIn this study, we aimed to elucidate the restorative effects of olfactory epithelium neural stem cells (oe-NSCs) implantation on noise-induced hearing loss and establish their mechanism of action. MethodsTo model hearing loss, rats were subjected to consecutive seven-day noise exposure. Then, oe-NSCs were implanted into cochlear tissue by retroauricular approach. Auditory brainstem response (ABR) method was used to evaluate the hearing function. Immunohistochemical staining was utilized to determine cell survival and migration of oe-NSCs. After IL-1β stimulation, nerve growth factor (NGF), neurotrophin-3 (NT-3), and NT-4 levels were evaluated in oe-NSCs. The protective action of oe-NSCs against hydrogen peroxide-induced cell injury was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Resultsoe-NSCs implantation into cochlear tissues ameliorated the noise-induced hearing impairment (p<0.05). After implantation, green fluorescent cells were observed in an even suspension in the lymph fluid of the cochlea, and 65% of the GFP+ cells reached the cochlear duct wall three days after implantation, but did not expand to the Corti-organ. After IL-1β stimulation, olfactory epithelial stem cell increased their secretion of NGF and NT-3 (p<0.05), but not that of NT-4. TUNEL assay results revealed that oe-NSCs co-culturing with injured neurons reduced the apoptotic cell death induced by hydrogen peroxide. ConclusionAfter transplantation into the inner ear, oe-NSCs not only survived, but also migrated around the spiral ganglion neurons (SGNs) in Rosenthal's canal (RC). Hearing loss induced by noise exposure was restored after oe-NSCs implantation. Mechanically, oe-NSCs secreted NGF and NT-3, which likely contributed to the prevention of neuronal injury. This study provides novel data in support of the effective action of implanted oe-NSCs in the restoration of noise-induced hearing loss in a rat model.

The Effect of Atorvastatin on Preventing Noise-Induced Hearing Loss: An Experimental Study.

Background:Noise-induced hearing loss (NIHL) is a common, irreversible occupational disease. Statins have recently been proposed to prevent NIHL.Objective:To assess the effect of atorvastatin for the prevention of NIHL in rats.Methods:In this experimental study, forty 2–3-month-old Wistar male rats were divided into 5 groups of 8 animals. 3 groups of rats received atorvastatin at doses of 5, 25, and 50 mg/kg daily for 14 days. The 4th group of rats received normal saline; another group was the control group. After 2 weeks of treatment, the rats were exposed to broad-band noise (125– 20 000 Hz) at 110 dB-SPL intensity for 2 hours. Response amplitude of all ears at 5 frequencies was assessed by distortion product otoacoustic emissions (DP-OAE) at baseline, 2 hours, and 2 weeks after the exposure.Results:Response amplitude was significantly decreased at all frequencies immediately after exposure to noise in all studied groups. The amplitude increased after 72 hours to a level higher than temporary threshold shift (TTS); this change was only significant in the group received 5 mg/kg atorvastatin.Conclusion:Low dose atorvastatin (5 mg/kg) used before exposure to noise can probably prevent NIHL in rats. This effect was not observed with higher doses of the drug.

Low-level laser therapy for prevention of noise-induced hearing loss in rats

Noninvasive low-level laser therapy (LLLT) is neuroprotective, but the mechanism of this effect is not fully understood. In this study, the use of LLLT as a novel treatment for noise-induced hearing loss (NIHL) is investigated. Sprague–Dawley rats were exposed to intense noise and their right ears were irradiated with an 808nm diode laser at an output power density of 110 or 165mW/cm2 for a 30min period for 5 consecutive days. Measurement of the auditory brainstem response revealed an accelerated recovery of auditory function in the groups treated with LLLT compared with the non-treatment group at days 2, 4, 7 and 14 after noise exposure. Morphological observations also revealed a significantly higher outer hair cell survival rate in the LLLT groups. Immunohistochemical analyses for inducible nitric oxide synthase (iNOS) and cleaved caspase-3 were used to examine oxidative stress and apoptosis. Strong immunoreactivities were observed in the inner ear tissues of the non-treatment group, whereas these signals were decreased in the LLLT group at 165mW/cm2 power density. Our findings suggest that LLLT has cytoprotective effects against NIHL via the inhibition of iNOS expression and apoptosis.

Subchronic Jp-8 Jet Fuel Exposure Enhances Vulnerability To Noise-Induced Hearing Loss In Rats

Both laboratory and epidemiological studies published over the past two decades have identified the risk of excess hearing loss when specific chemical contaminants are present along with noise. The objective of this study was to evaluate the potency of JP-8 jet fuel to enhance noise-induced hearing loss (NIHL) using inhalation exposure to fuel and simultaneous exposure to either continuous or intermittent noise exposure over a 4-wk exposure period using both male and female Fischer 344 rats. In the initial study, male (n = 5) and female (n = 5) rats received inhalation exposure to JP-8 fuel for 6 h/d, 5 d/wk for 4 wk at concentrations of 200, 750, or 1500 mg/m3. Parallel groups of rats also received nondamaging noise (constant octave band noise at 85 dBlin) in combination with the fuel, noise alone (75, 85, or 95 dB), or no exposure to fuel or noise. Significant concentration-related impairment of auditory function measured by distortion product otoacoustic emissions (DPOAE) and compound action potential (CAP) threshold was seen in rats exposed to combined JP-8 plus noise exposure when JP-8 levels of 1500 mg/m3 were presented with trends toward impairment seen with 750 mg/m3 JP-8 + noise. JP-8 alone exerted no significant effect on auditory function. In addition, noise was able to disrupt the DPOAE and increase auditory thresholds only when noise exposure was at 95 dB. In a subsequent study, male (n = 5 per group) and female (n = 5 per group) rats received 1000 mg/m3 JP-8 for 6 h/d, 5 d/wk for 4 wk with and without exposure to 102 dB octave band noise that was present for 15 min out of each hour (total noise duration 90 min). Comparisons were made to rats receiving only noise, and thosereceiving no experimental treatment. Significant impairment of auditory thresholds especially for high-frequency tones was identified in the male rats receiving combined treatment. This study provides a basis for estimating excessive hearing loss under conditions of subchronic JP-8 jet fuel exposure.

Have You Heard About Levitra?

The type 5 phosphodiesterase inhibitor Levitra (vardenafil) prevents noise-induced hearing loss in rats.

The combined effect of noise and carbon monoxide on hearing thresholds of exposed workers

Animal models have been used to demonstrate the potentiation of noise-induced hearing loss (NIHL) by carbon monoxide. It has been shown that the addition of carbon monoxide to otherwise safe noise exposure levels produces significant NIHL in rats. However, the effects of chronic exposure to low level of carbon monoxide in a noisy work environment are still unknown. The aim of this study was to compare the hearing thresholds of a group of workers exposed to noise and carbon monoxide (Group 1) to another group of workers where carbon monoxide exposure is absent or negligible (Group 2). The analysis was based on 9396 audiograms collected by the Quebec National Public Health Institute between 1983 and 1996. The results show significantly poorer hearing thresholds at high frequencies (3, 4, and 6 kHz) for the carbon monoxide exposed group (p&amp;lt;0.001). The potentiation effect also varied according to years of exposure in work place; a larger effect is observed for workers with between 15 to 20 years of exposure (p&amp;lt;0.001). This study provides the first demonstration of a potentiation effect of NIHL by carbon monoxide in humans.

Ebselen-mediated protection from single and repeated noise exposure in rat.

Ebselen, a glutathione peroxidase mimic, is a candidate compound for the prevention of noise-induced hearing loss. Single-blinded, placebo-controlled study. Methods included single and repeated noise exposures on F-344 female rats given oral or injected ebselen or vehicle before and after noise, evoked auditory brainstem responses using click and pure-tone stimuli, light and fluorescence microscopy of cochleae stained with 4',6-Diamidino-2-phenylindole (DAPI) and fluorescein isothiocyanate-phalloidin, and statistical power determined by ANOVA. Auditory brainstem response indicated that ebselen provided significant protection from both temporary and permanent threshold shifts following single and repeated noise exposure. On average, three times more outer hair cells were lost in control versus ebselen-treated animals. Ebselen reduces noise-induced hearing loss in rats.

Acrylonitrile Potentiates Noise-Induced Hearing Loss in Rat

Acrylonitrile, one of the 50 most commonly produced industrial chemicals, has recently been identified as a promoter of noise-induced hearing loss (NIHL). This agent has the potential to produce oxidative stress through multiple pathways. We hypothesize that acrylonitrile potentiates NIHL as a consequence of oxidative stress. The objectives of this study were to characterize acrylonitrile exposure conditions that promote permanent NIHL in rats and determine the ability of this nitrile to produce auditory dysfunction by itself. Additionally, we sought to determine whether a spin-trap agent that can form adducts with ROS would protect against the effects of acrylonitrile. Acrylonitrile administration produced significant elevation in NIHL detected as a loss in compound action potential sensitivity. The effect was particularly robust for high-frequency tones and particularly when acrylonitrile and noise were given on repeated occasions. Acrylonitrile by itself did not disrupt threshold sensitivity. Administration of the spin-trap agent phenyl- N- tert-butylnitrone (PBN), given to rats prior to acrylonitrile and noise, did block the elevation of NIHL by acrylonitrile. However, PBN at the dose and time interval given was ineffective in protecting auditory function in subjects exposed to noise alone. The results suggest that oxidative stress may play a role in the promotion of NIHL by acrylonitrile.

Noise-induced hearing loss in rats with renal hypertension

Genetically hypertensive rats have been found in previous studies to be more susceptible than normotensive rats to the formation of lesions of the inner ear as a result of excess noise. The present study was designed to investigate whether or not that susceptibility is a direct result of the high blood pressure. Hypertension was induced in 28 Sprague-Dawley rats by placing a 0.25 mm wide silver clip on one renal artery. Systolic blood pressure was measured indirectly by a tail-cuff technique 3 weeks after the operation and again after noise exposure. The animals were kept for one month in noise conditions (100 dB Leq (lin)) simulating those in an industrial milieu. The frequency range was adjusted to correlate to the hearing range of the rat. Auditory sensitivity was assessed electrophysiologically by recording auditory brain stem response to pulses of 1/3-octave filtered full-cycle sine waves. The results showed no correlation between hearing loss and systolic blood pressure. There was no difference between the audiograms obtained from rats with a systolic pressure below 160 mmHg and those obtained from rats with systolic pressures of between 170 and 255 mmHg. These results do not support the hypothesis that high blood pressure is a mechanism underlying noise-induced hearing loss.