Sunday 29 September 2013

New breakthroughs in pathophysiology and treatment for Noise Induced Hearing Loss (NIHL)


It's easy to say that we should avoid loud noises, but in reality, this is not always possible. Front-line soldiers or first responders do not have time to worry about the long-term effects of loud noise when they are giving their all. If, however, a drug could be developed to minimize the negative effects of loud noises, it would benefit one and all.

Noise-induced hearing loss, with accompanying tinnitus and sound hypersensitivity is a common condition which leads to communication problems and social isolation.

In a research report published in the September 2013 issue of The FASEB Journal, scientists describe exactly what type of damage noise does to the inner ear, and provide insights into a compound that may prevent noise-related damage.

To make this discovery, Shi and colleagues used three groups of 6 - 8 week old mice, which consisted of a control group, a group exposed to broadband noise at 120 decibels for three hours a day for two days, and a third group given single-dose injections of pigment epithelium-derived factor (PEDF) prior to noise exposure. PEDF is a protein found in vertebrates that is currently being researched for the treatment of diseases like heart disease and cancer. The cells that secrete PEDF in control animals showed a characteristic branched morphology, with the cells arranging in a self-avoidance pattern which provided good coverage of the capillary wall. The morphology of the same cells in the animals exposed to wide-band noise, however, showed clear differences -- noise exposure caused changes in melanocytes located in the inner ear.

At the present time, the only treatment strategies for hearing loss are hearing aids and cochlear implants. Drug therapies for noise-induced hearing loss have only recently been proposed and, to date, there are virtually no treatments that can repair the damage to the inner ear and reduce the impact of hearing loss.

Researchers from the University of Auckland, New Zealand, have discovered that a potent new drug restores hearing after noise-induced hearing loss in rats. The landmark discovery found that injection of an agent called 'ADAC', activates adenosine receptors in cochlear tissues, resulting in recovery of hearing function.

Vlajkovic and his team's study investigates the potential of adenosine amine congener (ADAC) -- a selective A1 adenosine receptor agonist -- in the treatment of noise-induced hearing loss. Wistar rats were exposed to narrow-band noise for 2 -- 24 hours in an acoustic chamber to induce cochlear damage and permanent hearing loss. ADAC or placebo control was then administered by injection(s) in the abdomen, either as a single injection at six hours or multiple daily injections. The researchers measured the hearing in the rats before and after the treatments using a technique known as auditory brainstem response (ABR). They also used histological techniques to determine the number of missing cochlear sensory hair cells after noise exposure and the noise-induced production of free radicals.

Their results show that cochlear injury and hearing loss in rats exposed to narrow-band noise can be substantially restored by ADAC administration after noise exposure. Early treatment starting six hours after noise exposure was the most effective and provided greater recovery than late treatment starting 24 hours after noise exposure. The most sustainable treatment strategy was the one involving multiple injections of ADAC for five days after noise exposure. This therapy significantly attenuated noise-induced hearing loss and improved sensory hair cell survival.

Resveratrol, a substance found in red grapes and red wine, may have the potential to protect against hearing and cognitive decline, according to a published laboratory study from Henry Ford Hospital in Detroit.

The study shows that healthy rats are less likely to suffer the long-term effects of noise-induced hearing loss when given resveratrol before being exposed to loud noise for a long period of time. Resveratrol is a very powerful chemical that seems to protect against the body's inflammatory process as it relates to aging, cognition and hearing loss. The latest study focuses on the inflammatory process as it relates to aging, cognition and hearing loss.

It was designed to identify the potential protective mechanism of resveratrol following noise exposure by measuring its effect on cyclooxygenase-2 (or COX-2, key to the inflammatory process) protein expression and formation of reactive oxygen species, which plays an important role in cell signaling and homeostasis.

The study reveals that acoustic over-stimulation causes a time-dependent, up-regulation of COX-2 protein expression, and, resveratrol, significantly reduces reactive oxygen species formation, inhibits COX-2 expression and reduces noise-induced hearing loss following noise exposure in rats. Ultimately, these findings suggest that resveratrol may exert a protective effect from noise-induced hearing loss by the inhibition of COX-2 expression and reactive oxygen species formation, although other mechanism may also be involved.

An epilepsy drug shows promise in an animal model at preventing tinnitus from developing after exposure to loud noise, according to a new study by researchers at the University of Pittsburgh School of Medicine.

The team focused on an area of the brain that is home to an important auditory center called the dorsal cochlear nucleus (DCN). From previous research in a mouse model, they knew that tinnitus is associated with hyperactivity of DCN cells -- they fire impulses even when there is no actual sound to perceive. For the new experiments, they took a close look at the biophysical properties of tiny channels, called KCNQ channels, through which potassium ions travel in and out of the cell.

They found that mice with tinnitus have hyperactive DCN cells because of a reduction in KCNQ potassium channel activity. These KCNQ channels act as effective "brakes" that reduce excitability or activity of neuronal cells.

Tzounopoulos and his team tested whether an FDA-approved epilepsy drug called retigabine, which specifically enhances KCNQ channel activity, could prevent the development of tinnitus. Thirty minutes into the noise exposure and twice daily for the next five days, half of the exposed group was given injections of retigabine. The researchers found that mice that were treated with retigabine immediately after noise exposure did not develop tinnitus.

Such a medication could be a very helpful preventive strategy for soldiers and other people who work in situations where exposure to very loud noise is likely,

Source:

  1. Federation of American Societies for Experimental Biology. "Now hear this: Scientists discover compound to prevent noise-related hearing loss." ScienceDaily, 29 Aug. 2013. Web. 29 Sep. 2013. 
  2. Srdjan M. Vlajkovic, Kyu-Hyun Lee, Ann Chi Yan Wong, Cindy X. Guo, Rita Gupta, Gary D. Housley, Peter R. Thorne.Adenosine amine congener mitigates noise-induced cochlear injury. Purinergic Signalling, 2010; DOI:10.1007/s11302-010-9188-5
  3. M. D. Seidman, W. Tang, V. U. Bai, N. Ahmad, H. Jiang, J. Media, N. Patel, C. J. Rubin, R. T. Standring. Resveratrol Decreases Noise-Induced Cyclooxygenase-2 Expression in the Rat Cochlea. Otolaryngology -- Head and Neck Surgery, 2013; DOI: 10.1177/0194599813475777
  4. J. W. Middleton, T. Kiritani, C. Pedersen, J. G. Turner, G. M. G. Shepherd, T. Tzounopoulos. Mice with behavioral evidence of tinnitus exhibit dorsal cochlear nucleus hyperactivity because of decreased GABAergic inhibitionProceedings of the National Academy of Sciences, 2011; 108 (18): 7601 DOI:10.1073/pnas.1100223108

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