The hearing process is reasonably straightforward.  As shown in Figure 1, sound pressure waves are funneled through the auditory meatus of the external ear (E).  These pressure waves mechanically deflect the tympanic membrane (in green), resulting in motion of three small bones in the middle ear (M).  One of these small bones, the stapes, rests against a membrane covered window into the snail-shaped cochlea, or inner ear (I).  Mechanical motion of the stapes results in fluid displacement in the cochlea, with fluid moving in waves corresponding to the pressure pulses of the sound waves.  In the cochlea is the sensitive organ of Corti, which is the acoustic interface of the nervous system.  Specialized cells in the organ of Corti translate the mechanical pressure impulses into electrical impulses which travel along the auditory nerve to the brain and produce a sensation of sound.  The organ of Corti contains two important types of inner ear sensory cells:  outer hair cells and the inner hair cells.  The outer hair cells can be thought of as the body’s microphone - they amplify motion produced in response to sound and enhance sensitivity to sound by some 30-40 db. These cells are highly susceptible to stress-induced injury caused by noise, drug, or other chemical exposure.  At the tops of the outer hair cells are rows of hair-like structures termed stereocilia.  The stereocilia are the “connection” between the outer and inner hair cells; motion of the outer hair cell stereocilia drives the inner hair cells to release a neurotransmitter, glutamate, which is the final step in the transduction of the mechanical response to an electrical impulse that the brain codes as sound.  Figure 2 shows a scanning electron micrograph of a portion of the organ of Corti, with outer hair cells clearly organized in upright rows (a single outer hair cell is labeled “O”).  The large upright cells on the bottom and the thinner diagonal cells across the front are support cells.  Also shown are bundles of stereocilia (the hair-like projections), connected to the outer hair cells, arranged in horizontal rows at the top of the picture. 

It is now well accepted that loud noise drives intense metabolic activity, which results in excess free radical formation in the cellular mitochondria of the inner ear.  Free radicals are molecules containing unpaired electrons.  The unpaired electron is a highly reactive “hot potato” that either “burns” a molecule (causes oxidative damage) or is passed from molecule to molecule, turning the recipient into a free radical and neutralizing the donor.  Such activity has been shown to destroy cellular membranes and modify gene expression in cochlear cells, leading to cell death and NIHL, as shown in Figure 3.  Extreme noise can also produce mechanical trauma as a direct result of sound-induced vibration that exceeds the limits of this hair cell system.  Prior to the mid-1990’s, when the important role of free radical production in noise-induced cell death first emerged, it was assumed that mechanical destruction of the organ of Corti structures was the primary cause of NIHL.

Protection From Hearing Damage

Studies in animals have now identified multiple mechanisms underlying NIHL, including direct mechanical trauma, free radicals formed in association with metabolic stress, and reduced blood flow.  In most tissues, increased metabolism increases blood flow, providing additional oxygen to stressed cells.  However, in the cochlea, high levels of noise reduce blood vessel diameter and thereby decrease blood flow.  Antioxidants, which attenuate free radical formation, and vasodilating agents, which increase blood flow, effectively reduce sensory cell death and NIHL in animal studies.  Among the antioxidants shown to be effective in reducing NIHL, as well as hearing loss induced by drugs and/or age, are vitamins A, C, and E.  With longer-term dosing (i.e., 10-13 days), each of these individual dietary antioxidant nutrients (already approved for human use) have small protective effects against many types of ototoxic (i.e., death of hair cells) insults in humans.  Magnesium supplements, which increase cochlear blood flow along with other effects, also provide some protection against NIHL in humans and animals with pre-treatment.  The primary antioxidant action of vitamin A is to scavenge singlet oxygen.  Singlet oxygen (the lowest excited state of the O2 molecule) reacts with lipids to form lipid hydroperoxides, so the removal of singlet oxygen prevents lipid peroxidation, a process whereby free radicals “steal” electrons from the lipids in our cell membranes, resulting in cell damage and increased production of free radicals.  Vitamin E, present in lipids in cells, is a donor antioxidant that reacts with and reduces peroxyl radicals and, thus, inhibits the propagation cycle of lipid peroxidation.  Vitamin C detoxifies free radicals by reducing (neutralizing) them.  Scavenging of oxygen radicals by Vitamin C occurs in the aqueous phase, in contrast to the site of action of vitamin E, within membranes.  Thus, these different antioxidant substances exert their actions at various points along a molecular pathway.  Whereas antioxidants reduce the presence of reactive oxygen species, magnesium reduces noise-induced vasoconstriction and may have additional beneficial effects.