Therapeutic effect of sildenafil on blast-induced tinnitus and auditory impairment

Mahmood, G.; Mei, Zhi-Gang; Hojjat, Houmehr; Pace, Edward; Kallakuri, Srinivasu; Zhang, J.S.

doi:10.1016/j.neuroscience.2014.03.020

Cited by 24 publications

(37 citation statements)

References 124 publications

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“…Tinnitus behavior manifested across a range of spectral frequencies, but most robustly at 26–28 kHz. Together, these trends match previous reports on animal models of blast- 52, 53, 65 and noise-induced tinnitus 66, 67 . These findings also reflect the clinical situation, in that tinnitus may not disappear over time following blast exposure 68 , and that blast exposure induces lasting tinnitus in some but not all individuals 8 .…”

Section: Discussionsupporting

confidence: 91%

“…Therefore, it is possible that blast influences emotional processing in animals by affecting their physiology. First, blast can cause an array of physiological damage, including vision, auditory and motor defects 49, 51, 65, 94, 95, 97 , and sustaining such damage may yield an emotional impact on animals. Second, TBI can be induced by blast wave exposure 98–101 and is itself a potential trigger for anxiety in both animals 102, 103 and humans 104, 105 .…”

Section: Discussionmentioning

confidence: 99%

“…Gap-detection and PPI testing were conducted before (3 times/week) and after (2 times/week) blast exposure to measure tinnitus behavior and hearing detection, as described elsewhere 52, 53, 65–67, 150 . Briefly, a rat was placed in a custom-made restrainer and locked onto a platform inside a sound-attenuation chamber (Kinder Scientific, Poway, CA).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Blast-Induced Tinnitus and Elevated Central Auditory and Limbic Activity in Rats: A Manganese-Enhanced MRI and Behavioral Study

Ouyang

Pace

Lepczyk

et al. 2017

Sci Rep

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Blast-induced tinitus is the number one service-connected disability that currently affects military personnel and veterans. To elucidate its underlying mechanisms, we subjected 13 Sprague Dawley adult rats to unilateral 14 psi blast exposure to induce tinnitus and measured auditory and limbic brain activity using manganese-enhanced MRI (MEMRI). Tinnitus was evaluated with a gap detection acoustic startle reflex paradigm, while hearing status was assessed with prepulse inhibition (PPI) and auditory brainstem responses (ABRs). Both anxiety and cognitive functioning were assessed using elevated plus maze and Morris water maze, respectively. Five weeks after blast exposure, 8 of the 13 blasted rats exhibited chronic tinnitus. While acoustic PPI remained intact and ABR thresholds recovered, the ABR wave P1-N1 amplitude reduction persisted in all blast-exposed rats. No differences in spatial cognition were observed, but blasted rats as a whole exhibited increased anxiety. MEMRI data revealed a bilateral increase in activity along the auditory pathway and in certain limbic regions of rats with tinnitus compared to age-matched controls. Taken together, our data suggest that while blast-induced tinnitus may play a role in auditory and limbic hyperactivity, the non-auditory effects of blast and potential traumatic brain injury may also exert an effect.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Blast-Induced Tinnitus and Elevated Central Auditory and Limbic Activity in Rats: A Manganese-Enhanced MRI and Behavioral Study

Ouyang

Pace

Lepczyk

et al. 2017

Sci Rep

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“…Namely, the increase in CBS levels observed with age may be necessary for the production of H 2 S, which is a regulator of the synthesis of anti- and pro-oxidant enzymes and mediators of inflammation (Ingenbleek and Kimura, 2013; Kabil et al, 2014a,b). In fact, it is known that various synthetic drugs, which supply this gas, have been used for the treatment of deafness with variable results (Lamm and Arnold, 1998; Mahmood et al, 2014). CBS also contributes to cysteine synthesis, a semi-essential proteinogenic amino acid that is mostly obtained from the diet although a 50% of that synthesized through transuslfuration is used in GSH synthesis.…”

Section: Nutritional Interventions and Hearing Lossmentioning

confidence: 99%

Cochlear Homocysteine Metabolism at the Crossroad of Nutrition and Sensorineural Hearing Loss

Partearroyo

Vallecillo

Pajares

et al. 2017

Front. Mol. Neurosci.

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Hearing loss (HL) is one of the most common causes of disability, affecting 360 million people according to the World Health Organization (WHO). HL is most frequently of sensorineural origin, being caused by the irreversible loss of hair cells and/or spiral ganglion neurons. The etiology of sensorineural HL (SNHL) is multifactorial, with genetic and environmental factors such as noise, ototoxic substances and aging playing a role. The nutritional status is central in aging disability, but the interplay between nutrition and SNHL has only recently gained attention. Dietary supplementation could therefore constitute the first step for the prevention and potential repair of hearing damage before it reaches irreversibility. In this context, different epidemiological studies have shown correlations among the nutritional condition, increased total plasma homocysteine (tHcy) and SNHL. Several human genetic rare diseases are also associated with homocysteine (Hcy) metabolism and SNHL confirming this potential link. Accordingly, rodent experimental models have provided the molecular basis to understand the observed effects. Thus, increased tHcy levels and vitamin deficiencies, such as folic acid (FA), have been linked with SNHL, whereas long-term dietary supplementation with omega-3 fatty acids improved Hcy metabolism, cell survival and hearing acuity. Furthermore, pharmacological supplementations with the anti-oxidant fumaric acid that targets Hcy metabolism also improved SNHL. Overall these results strongly suggest that cochlear Hcy metabolism is a key player in the onset and progression of SNHL, opening the way for the design of prospective nutritional therapies.

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“…These results imply that as the level of CTS increases, there is progressively less neural activity or neural synchronization occurring within the auditory brainstem, that is, neural hypoactivity. An important theoretical and clinically relevant question posed by these results is do subjects in a state of CTS experience loudness decruitment (abnormally slow loudness growth) similar to patients with acoustic neuromas or brain damage (Hebert et al, 2013, Dawes et al, 2014) or do they experience loudness recruitment characteristic of patients with sensorineural hearing loss or hyperacusis that is often associated with tinnitus (Loeb and Smith, 1967, Martins et al, 2013, Mahmood et al, 2014)?…”

Section: Discussionmentioning

confidence: 99%

Prolonged noise exposure-induced auditory threshold shifts in rats

et al. 2014

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Noise-induced hearing loss (NIHL) initially increases with exposure duration, but eventually reaches an asymptotic threshold shift (ATS) once the exposure duration exceeds 18-24 h. Equations for predicting the ATS have been developed for several species, but not for rats, even though this species is extensively used in noise exposure research. To fill this void, we exposed rats to narrowband noise (NBN, 16-20 kHz) for 5 weeks starting at 80 dB SPL in the first week and then increasing the level by 6 dB per week to a final level of 104 dB SPL. Auditory brainstem responses (ABR) were recorded before, during, and following the exposure to determine the amount of hearing loss. The noise induced threshold shift to continuous long-term exposure, defined as compound threshold shift (CTS), within and above 16-20 kHz increased with noise level at the rate of 1.82 dB threshold shift per dB of noise level (NL) above a critical level (C) of 77.2 dB SPL i.e. CTS = 1.82(NL-77.2). The normalized amplitude of the largest ABR peak measured at 100 dB SPL decreased at the rate of 3.1% per dB of NL above the critical level of 76.9 dB SPL, i.e., %ABR Reduction = 3.1%(NL-76.9). ABR thresholds measured >30 days post-exposure only partially recovered resulting in a permanent threshold shift of 30-40 dB along with severe hair cell loss in the basal, high-frequency region of the cochlea. In the rat, CTS increases with noise level with a slope similar to humans and chinchillas. The critical level (C) in the rat is similar to that of humans, but higher than that of chinchillas.

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Therapeutic effect of sildenafil on blast-induced tinnitus and auditory impairment

Cited by 24 publications

References 124 publications

Blast-Induced Tinnitus and Elevated Central Auditory and Limbic Activity in Rats: A Manganese-Enhanced MRI and Behavioral Study

Blast-Induced Tinnitus and Elevated Central Auditory and Limbic Activity in Rats: A Manganese-Enhanced MRI and Behavioral Study

Cochlear Homocysteine Metabolism at the Crossroad of Nutrition and Sensorineural Hearing Loss

Prolonged noise exposure-induced auditory threshold shifts in rats

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