Overview of mechanical damage to the inner ear: noise as a tool to probe cochlear function

Hearing Research, 22 (1986) 307-321 Elsevier

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Overview of mechanical damage to the inner ear: noise as a tool to probe cochlear function Norma Slepecky Institute for Sensory Research, Syracuse University, Syracuse, NY 13210, and Deparzment Anatomy and Ceil Bioiogv, iJpstate Medicat Center, Syracuse, NY i 3210, U.S. A.

The majority of experiments causing mechanical damage to the cochlea involve the use of sound pressure waves to cause overstimulation. This presentation is an overview of the research during the past years on the structural damage produced by noise. The effect of noise on the cochlea depends on the type of noise exposure - impulse or continuous. Experiments have been conducted to determine the effect of increasing intensity, the effect of increasing duration, and the effect of equal energy presented over varying periods of time. The initial mechanism of damage, the progression of damage over time, and the ability of hair cells to recover are discussed. Noise has been used as a tool to probe cochlear function by selectively damaging regions along the length of the sensory epithelium and by selectively damaging one of the two types of hair cells. Results obtained from these types of experiments have given us information on cochlear mechanics, as well as of stereocilia microm~hani~ and transduction. Information on susceptibility of hair cells to noise confirms previous results, suggesting the presence of structural and metabolic gradients both lon~tudinaliy and radially within the sensory epithehum. Moreover, noise lesions have been used to map the afferent innervation pattern to the cochlear nucleus, and noise studies show correlation of hair cell damage with efferent innervation pattern.

Introduction

Types of noise

The majority of experiments causing mechanical damage to the cochlea involve the use of sound pressure waves to cause overstimulation. Several excellent reviews on the effects of noise on the inner ear have been published in the last few years (Henderson et al., 1976; Hamernik et al., 1982; Schmiedt, 1985; Saunders et al., 1985b) that discuss in detail the specific damage caused by different types of noise, and integrate the experimental results in the areas of anatomy, biochemistry and physiology with the changes in hearing known to occur after such trauma. It is the aim of this presentation to give a general overview of what is known about the ways that noise and mechanically induced lesions affect the cochlea, and to discuss what the damage produced from these types of experimental manipulations has told us about inner ear function.

The effect of noise on the cochlea depends on the type of noise used. Impulse and impact noise are characterized by high intensity and short duration, and can produce immediate mechanical alterations to the cochlea. Using surface preparations observed with the light microscope and using specimens prepared for scanning electron microscopy, it has been observed that there may be tears in Reissner’s membrane and the basilar membrane. There are focal lesions where the impulse waves have caused almost total destruction of areas along the sensory epithehum as shown in Fig. la (Hame~k et al., 1984b). After longer times post-exposure, in areas previously not displaying immediate damage, there may be large lesions where all hair cells and supporting cells are missing (Poche et al., 1969; Jordan et al., 1973b; Henderson et al., 1974; Erlandsson et al., 1980; Hunter-Duvar et al., 1982; Lim et al., 1982). It is difficult to predict the extent of damage produced by increasing exposure to impulse noise

* Correspondence: stitute,

Department S-10401, Stockholm,

0378-5955/86/$03,50

Physiology Sweden.

II, Karolinska

0 1986 Elsevier Science Publishers

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B.V. (Biomedical

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because often the exact parameters of the exposure that reaches the sensory epithelium cannot be certain. The middle ear may be damaged and the tympanic membrane torn, affecting the conduction system. Because the organ of Corti is often destroyed early in the exposure, the pattern of basilar membrane motion and the micromechanical properties of the remaining hair cell stereociliatectorial membrane interactions may be affected. Breaks between sensory and supporting cells may cause a mechanical decoupling of the organ of Corti from the motion of the basilar membrane. All such mechanical damage has serious implications for the transmission of the stimulus over long periods of time. Moreover, the analysis of the purely mechanical effects of impulse noise trauma are complicated by the fact that there are secondary alterations resulting from the intermixing of the cochlear fluids, the change in the metabolism of the remaining supporting and sensory cells, and physical disruption of the vasculature. Continuous noise has been used more often to establish the relationship between noise and damage to the inner ear. In cases where damage to the cochlea is from exposure to lower levels of noise, the organ of Corti does not detach from the basilar membrane, but sensory cells degenerate leaving scars (Fig. lc) where supporting cells have expanded to fill their place (Stockwell et al., 1969; Bohne, 1971). The location of damage depends on the frequency composition of the stimulus, and the extent of damage depends on stimulus intensity and duration. Experiments varying these parameters have been used to study the immediate effects of noise, the progression of changes within a hair cell leading to hair cell death, and the changes to areas bordering the initial lesioned area which might explain the growth of the lesion over time post-exposure. Although results from these experiments do not allow direct comparisons between species (Hunter-Duvar and Bredberg, 1974; Saunders and Tilney, 1982) information gained

from such studies has allowed us to speculate on some of the mechanisms by which hair cells are damaged and suggests that some types of damage to hair cells may be reversible. Location of damage One of the earliest experiments with noise was designed specifically to determine what could be learned about the frequency analytical function of the cochlea from patterns of hair cell damage (Stockwell et al., 1969). It was expected that the position of the lesion produced by exposure to high intensity pure tone or narrow band noise would confirm the place-frequency experiments initiated by BCkCsy (1960) which demonstrated that the position of the maximum amplitude of the travelling wave varied along the length of the basilar membrane as a function of frequency. Extensions of this method using analysis of specimens prepared for surface preparations, transmission and scanning electron microscopy, and spiral ganglion and eighth nerve recordings have been used to map areas of damage caused by overstimulation to obtain place-frequency maps in several animal species (Liberman and Kiang, 1978; Cody et al., 1980; Engstrom and Borg, 1981; Eldridge et al., 1981; Ryals and Rubel, 1982). The mechanisms responsible for determining the frequency selectivity of the sensory epithelium are not completely known but are thought to be determined by the mechanical properties of the basilar membrane-organ of Corti-tectorial membrane complex. The results of experiments on the developing chick basilar papilla, using pure-tone noise exposures support some form of mechanical tuning (Rubel and Ryals, 1983). During development, there is a systematic shift in the position of hair cell damage toward the apex of the cochlea, produced by each of three frequencies. This suggests that the part of the sensory epithelium that is maximally responsive to a particular frequency

Fig. 1. Damage to the organ of Corti after noise trauma. (la) Immediately after high intensity impulse noise, part of the organ of Corti containing the outer hair cells is blown off the basilar membrane. From Hamernik et al. (1984a), with permission. (lb) Immediately after lower intensity noise, holes are present in the reticular lamina where outer hair cells have been destroyed, and endolymph can communicate with fluid filled spaces of the organ of Corti. From Bohne and Rabbit (1983). with permission. (lc) At longer times post-exposure, scars have formed on the reticular lamina in the place of the missing outer hair cells. From Bohne and Rabbit (1983). with permission. (Id) At longer times post-exposure, there may be loss of the sensory and supporting cells, but the tectorial membrane remains intact. From Bredberg et al. (1972) with permission.

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sound shifts during development. If the place-frequency map shifts during development as a result of some sort of mechanical change as the organ of Corti matures structurally, the data supports the suggestion that mechanical properties of the organ of Corti contribute to the frequency selectivity of the sensory epithelium (Lim, 1980).

Effects of increasing time of exposure and intensity Initially, the experiments studying the effects of noise on the cochlea were used to determine the total amount of damage caused by a particular exposure, and hair cells were evaluated weeks or months after the noise exposure. This is an issue

Fig. 2. Damage to inner hair cell stereocilia after noise trauma. (2a) Fusion of the tallest stereocilia and loss of some of the shorter stereocilia. From Hunter-Duvar, with permission. (Zb) Floppy stereocilia. From Hunter-Duvar, with permission. (2~) Splayed stereocilia on inner hair cells, while stereocilia on outer hair cells are normal. From Hunter-Duvar, with permission. (2d) Damaged stereocilia on inner hair cells while stereocilia on outer hair cells are normal. From Engstrijm and Borg (1983) with permission.

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that is of tremendous importance in the work place where prevention of hearing loss is of primary concern. In general, for a given noise intensity, using pure tones and narrow bands, the amount of damage measured at 30 days post-exposure increases as the time of exposure increases (Spoendlin and Brun, 1973; Bohne and Clark, 1982). Using noise exposures of increasing intensity, no simple relation seems to exist between exposure intensity levels and the extent of structural damage. For a specific stimulus, and for one animal species, there appear to be two critical intensities - one below which practically no damage is produced, and one above which purely mechanical damage is obvious immediately after noise exposure (Spoendlin, 1976). In the region between these critical intensities, as intensity of exposure increases, permanent cochlear damage can be seen both structurally and functionally. Progression of hair cell damage At very short times after noise trauma, outer hair cells are swollen, show an accumulation of lysosomes, vacuolization of the endoplasmic reticulum and an increase in Hensen bodies (Engstrom and Ades, 1960; Spoendlin, 1962,1971; Beagley, 1965b; Lim and Melnick, 1971; Ward and Duvall, 1971). Stereocilia can undergo rapid changes immediately after noise when there do not appear to be any other ultrastructural changes occurring inside the cell (Spoendlin, 1971). Various forms of stereocilia damage are shown in Figs. 2 and 3. Clumping and fusion of stereocilia is observed immediately after noise exposure (Spoendlin, 1971; Hunter-Duvar, 1977; Robertson and Johnson, 1980) and can be seen months (Lindeman and Bredberg, 1972; Soudijn, 1976; Robertson et al., 1980b; Slepecky et al., 1982; Engstrom et al., 1983) or even years (Spoendlin, 1976; Liberman and Beil, 1979) post-exposure. Floppy stereocilia (Hunter-Duvar, 1977; Lim, 1980; Erlandsson et al., 1980) and stereocilia where cross-bridges between actin filaments have been broken (Tilney et al., 1982) or actin filaments are depolymerized (Tilney et al., 1982) are observed immediately after noise exposure, but there is some evidence that these are reversible changes. When suspected lesion areas are observed several days

after noise exposure, floppy stereocilia are not present (Hunter-Duvar, 1977) and stereocilia without actin filament cross-bridges cannot be found (Tilney et al., 1982). After longer survival times, more permanent changes to the stereocilia include: the presence of membrane blebs and membrane wrinkling (Lim and Melnick, 1971; Bredberg et al., 1972; Slepecky et al., 1982); stereocilia disarray (Lindeman and Bredberg, 1972; Hunter-Duvar, 1977; Liberman and Kiang, 1978; Liberman and Beil, 1979; Robertson et al., 1980b; Mulroy and Curley, 1982) and splaying (Hunter-Duvar et al., 1982); and formation of giant hairs (Lim and Melnick, 1971; Ward and Duvall, 1971; Bredberg et al., 1972; Lindeman and Bredberg, 1972; Engstrom et al., 1983). The rootlet of the relatively normal appearing stereocilia may be broken (Engstrom et al., 1983; Tilney et al., 1982), and in stereocilia where membrane fusion and actin filament depolymerization has been observed, the rootlet can disappear (Slepecky et al., 1982). Often all these changes are apparent in only the tallest of the stereocilia. The cuticular plate is extensively deformed after noise exposure (Lim and Melnick, 1971; Lindeman and Bredberg, 1972). The hair cell bodies become distorted, the cells lyse and debris can be found scattered in the spaces of Nuell and in Scala media (Bohne, 1971). It should be noted that the tectorial membrane appears resistant to damage (Fig. Id). It remains in the position seen normally in processed specimens long after noise exposure (Bredberg et al., 1972), in spite of degeneration of the underlying organ of Corti. Imprints of the site of attachment of the outer hair cell tall stereocilia remain on the tectorial membrane even after long term permanent damage to the organ of Corti (Hunter-Duvar, 1977). Minimum damage Since hair cells are the receptor cells and act as transducers of the sound energy in hearing, loss of the hair cells has commonly been used as a measure of damage. There are many studies where the loss of outer hair cells correlated with shifts in hearing thresholds of 40-50 dB (Beagley, 1965; Ades et al., 1974; Moody et al., 1976; Ryan and

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Bone, 1978; Stebbins et al., 1979). However, acoustic trauma does not always produce a consistent relationship between cochlear hair cell loss and hearing loss in experimental animals. In some cases there are functional losses when hair cells are present (Spoendlin, 1971; Hunter-Duvar and Elliott, 1972, 1973; Bohne et al., 1973; Kiang et al., 1976; Hamernik et al., 1980b). Detailed analysis beyond the surface preparation has shown, however, that there are other changes within the organ of Corti, other than missing sensory cells, that could account for the functional changes. The minimum structural damage that correlates with altered thresholds and frequency sensitivity occurs at the level of the stereocilia. Changes in behavioral thresholds and elevation of N, thresholds have been correlated with alterations to outer hair cell stereocilia (Robertson and Johnstone, 1980; Slepecky et al., 1982). Deficits in threshold of single nerve fibers and changes in behavioural threshold have also been correlated with changes in the stereocilia of inner hair cells (Liberman and Beil, 1979; Engstrom and Borg, 1983; Liberman, 1984). It is suggested that as stereocilia damage worsens from disarray, to partial fusion or loss, to total fusion or loss, the threshold shift increases (Slepecky et al., 1982; Liberman and Mulroy, 1982). Mechanisms

of damage

It is not surprising that high intensity sounds cause severe damage to the organ of Corti, since the sound pressure waves may cause violent motion of the basilar membrane causing tears in the basilar membrane, Reissner’s membrane (Lawrence and Yantis, 1957: Eldredge et al., 1957) or the reticular lamina (Beagley, 1965b; Jordan et al.. 1973b). Immediate damage to stereocilia may be mechanical in origin, causing collision of stereocilia of one cell with those on an adjacent cell

(Hunter-Duvar et al., 1982), or causing fusion of adjacent stereocilia on one sensory cell (Flock et al., 1977). Secondary effects to the remaining cells depend on the initial amount of mechanical damage and may be caused by the intermixing of cochlear fluids (Duvall and Rhodes, 1967; Duvall et al., 1969), changes to the vascular system causing damage by ischemia (Perlman et al., 1959; Jordan et al., 1973a; Bohne, 1976b), changes to supporting cells (Lindeman and Bredberg, 1972; Bohne, 1976a; Saunders and Tilney, 1982; Hamernik et al., 1984a), and general metabolic changes caused by overstimulation. More subtle forms of damage are caused by lower level noise exposures. Intermixing of cochlear fluids may still be a factor in causing hair cell pathologies, since low level noise may alter tight cell junctions at the reticular lamina or cause holes to appear in the reticular lamina (Bohne and Rabbit, 1983). both of which would provide a communication route between the endolymphatic space and fluid spaces of the organ of Corti (Fig. lb). Support for the effect of potassium rich endolymph reaching hair cell bodies and causing hair cell damage has come from perfusing the perilymphatic channels with artificial endolymph of varying ionic composition. The changes in cell morphology are similar to those observed following noise trauma (Bohne, 1976b). The effect of perilymph passing through these same channels and causing damage to the tectorial membrane (Kronester-Frei, 1979) and altering the micromechanical properties of the hair cell-stereociliatectorial membrane complex must also be considered. Damage specific to sensory cells may also result from metabolic stress and exhaustion due to increased load on the sensory cells, resulting in depletion of enzymes and metabolites. coupled to an insufficient or decreased circulation in the sensory regions. There are several lines of evidence

Fig. 3. Damage to outer hair cell stereocilia. (3a) Stereocilia with wrinkled membranes. From Slepecky et al. (1982). with permission. (3b) Flaccid stereocilia with blebs. From Slepecky et al. (1982),with permission. (3~) Stereocilium with broken rootlet. From Engstrijm et al. (1983). with permission. (3d) Stereocilia with membranes fused. From Engstrbm et al. (1983). with permission. (3e) Stereocilia where membranes have fused and rootlets have disappeared From Slepecky et al. (1982). with permission. (3f) Actin filaments within the core of the stereocitium of an alligator lizard where cross-bridges have broken. From Tilney et al. (1982). with permission. (3g) Actin filaments only at the tapered portion of the stereocilium of an alligator lizard have depolymerized and the stereocilium is bent. From Tilney et al. (1982), with permission.

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that suggest that metabolic damage occurs during noise trauma. Proliferation and vacuolization of the endoplasmic reticulum and swelling of mitochondria suggest that the high-energy yielding enzyme systems located on these internal membrane systems are rendered inoperative. There is an increase in the number of lysosomes at the apical surface of the hair cells. The enzyme activity of succinic dehydrogenase (Vosteen, 1961) and lactic dehydrogenase (Ishida, 1978; Omata et al., 1979) are changed by acoustic overstimulation. Glycogen in outer hair cells is diminished by prolonged sound exposure (Ishii et al., 1969). Evidence supporting increased metabolic activity has been obtained using 2-deoxyglucose. Acoustically stimulated increases in glucose utilization can be detected in sensory cell areas and in the auditory nerve, as well as in the tissues of the lateral wall after moderate intensity noise stimulation (Ryan et al.. 1982; Canlon and Schacht, 1983). Impaired circulation in the cochlear vessels during prolonged exposure is also suggested to contribute to the altered metabolism of the sensory cells. causing hair cell damage. It has not yet been established if there are changes in blood supply to the cochlea during noise exposure, and if they occur, what their relationship is to cochlear injury. Strial pathology is occasionally prominent (Lim and Melnick, 1971: Hawkins, 1973; Bohne et al., 1976) yet correlates poorly with the pattern of sensory cell damage (Bohne et al., 1976) and usually occurs after the first changes to the sensory cells have occurred (Duvall et al., 1974). Using microspheres to measure blood flow there are reports of no change (Angelborg et al., 1979; Hultcrantz, 1979) as well as reports of increased flow (Prazma et al., 1983). Others have looked for changes in the vasculature in vivo during noise exposure (Perlman and Kimura, 1962) and have observed slight increases and no evidence of strial pathology. Changes suggesting reduced blood flow that have been observed include narrowing of the diameters of exposed vessels by smooth muscle cells or pericytes (Lawrence et al., 1967; Hawkins, 1971: Lim and Melnick. 1971; Lipscomb and Roettger, 1973), cessation of blood flow as evidenced by the packing of red blood cells (Kellerhals, 1972) and changes in vascularity or avascular channels (Lawrence and Yantis, 1957:

Lawrence et al., 1967; Hawkins, 1971). By and large, the results have been conflicting, and the recent studies using the soft surface technique (reviewed in Axelsson and Vertes, 1982). using the laser Doppler technique (Miller et al., 1983) and using image analysis studies (Smith et al., 1985) may give more information as to how the changes in cochlear vasculature correlate with noise trauma to sensory cells. Susceptibility of hair cells to noise damage Stereociliu

Damage to stereocilia is immediate, mostly permanent and correlated with functional loss. The stereocilia may be vulnerable because they are long, thin, rigid structures, narrow at their base where they attach to the apical surface of the hair cell, and their function is to transmit mechanical stimuli. There are at least four distinct types of damage to stereocilia that have been reported, and the type of damage may tell us something about the various ways stereocilia function. Stereocilia fusion can occur immediately after high intensity sound. It is known that stereocilia cell coat material plays a role in maintaining normal stereocilia interactions (Pickles et al., 1984). It has been suggested that collision of adjacent stereocilia could overcome the electrostatic repulsion resulting from the electronegativity of the cell surface components, causing membrane fusion (Flock et al., 1979). Fusion may also indicate a general response to changes in cell metabolism since it is seen after ototoxic drug treatment as well as after noise. Stereocilia disarray may take several forms. Splaying suggests that the stereocilia can still be rigid, presumably with their rootlets intact, but that they are no longer in contact with each other. It has been suggested that the anatomical substrate for this type of damage is through cuticular plate-rootlet interactions (Slepecky and Chamberlain, 1982). Another form of stereocilia disarray may occur when stereocilia remain rigid. but are bent at an angle to the cuticular plate. The anatomical substrate for this type of damage may be rootlet breakage and depolymerization of the actin filaments in the rootlet area (Tilney et al., 1982). Floppy stereocilia have also been observed,

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where the stereocilia are no longer rigid but bend along their length, although the rootlets may be intact. An anatomical substrate for this type of damage may be the loss of cross-bridging between actin filaments (Tilney et al., 1982). Thus the damaging effects of noise suggest that there are several systems within the stereociliarootlet-cuticular plate complex which may regulate the stiffness of the stereocilia. If one measures stereocilia stiffness as the resistance to deflection (Flock and Orman, 1983; Flock and Strelioff, 1984), it is possible to predict mechanisms by which stiffness of stereocilia may either increase or decrease. If tension development occurs in the cuticular plate, which contains muscle-like contractile proteins (Flock et al., 1982; Drenckhahn et al., 1982; Slepecky and Chamberlain, 1986) putting the rootlets under stress or altering their normal position, resistance to deflection may increase. Experiments where hair cells have been exposed to media which cause contraction in muscle cells have in fact shown that such treatment causes an increase in stereocilia stiffness (Orman and Flock, 1983). If the rootlet has been decoupled from the distal tip of the stereocilium, stereocilia would offer less resistance to deflection. A similar phenomenon would occur if cross-bridges along the length of the stereocilium, thought to be fimbrin (Flock et al., 1982; Slepecky and Chamberlain, 1986) which is known to bundle actin filaments into stiff rods, are broken. The stereocilium would also offer less resistance if there is a change in the relationship of the actin and tropomyosin in the rootlet, where the function of tropomyosin may be to increase actin filament rigidity (Slepecky and Chamberlain, 1986). This predicted loss in stiffness may in fact occur during noise trauma. When stereocilia stiffness is measured after in vivo noise overstimulation (Miller et al., 1984) and in vitro mechanical overstimulation (Saunders and Flock, 1984), less force is necessary to move stereocilia a given distance. If the amount of displacement of stereocilia is proportional to hair cell response, then loss of stereocilia stiffness implies more displacement for a given force, thus greater response. However it could also be argued that the loss in stiffness might correspond to an increase in threshold mea-

sured after noise trauma. If the rootlet-lever arm function of the stereocilium (Saunders et al., 1985a) is compromised by decreased rigidity of the actin filaments or by the decoupling of the stereocilium from the rootlet, more movement would be required at the tip of the stereocilium to attain the necessary amount of stress or filament shear to activate transduction. It is interesting that there is some indication that floppy stereocilia may become erect (HunterDuvar, 1977), that cross-bridges between adjacent filaments may reform (Tilney et al., 1982) and that stiffness changes after overstimulation may be reversible (Miller et al., 1984; Saunders and Flock, 1984). Thus, some damage produced by noise trauma may be only temporary. The question remains if the interaction between the stereocilia and tectorial membrane may be reformed. Damage to stereocilia produced mechanically or by noise has shed light on the role played by stereocilia in the transduction process. Deflection of the stereocilia mediates the transduction process and mechanical manipulation of the stereocilia has demonstrated that the receptor potential within the hair cell is proportional to the number of stereocilia deflected (Hudspeth and Jacobs, 1979). This suggests that each stereocilium participates equally in the transduction event. Further support for this comes from experiments where the tallest stereocilia on inner hair cells have been damaged by noise. In eighth nerve fibers which contact these cells, spontaneous activity is reduced by one third (Liberman and Dodds, 1984). If the spontaneous activity is due to leakage current through transduction channels, this further suggests that each stereocilium has the same number of ion channels. Outer hair ceils are more susceptible Codamage than inner hair cells In general, the outer hair cells are more vulnerable to noise trauma than inner hair cells, regardless of the source of noise (Beagley, 1945a; Stockwell et al., 1969; Poche et al., 1969). There are many reasons why this might be expected. It may be for structural reasons. The inner hair cells are closer to the modiolus, sit closer to the osseous spiral lamina which does not move much during motion of the basilar membrane and are sur-

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rounded by supporting cells on all sides. Outer hair cells are located on that portion of the basilar membrane which vibrates with sound stimulus, they are coupled to the motion of the basilar membrane through the supporting cell so they move more than inner hair cells, they are coupled to the tectorial membrane through their tallest stereocilia so they may be subjected to mechanical damage at their apical surface, and as they are not surrounded by supporting cells they are more exposed to fluid motion. Support for mechanical damage of outer hair cells and protection of inner hair cells comes from experiments with impulse noise where outer hair cells are blown off the basilar membrane but inner hair cells look normal and apparently unaffected by severe damage (Hamernik et al.. 1984b). When lower levels of noise exposure are used, outer hair cells are damaged first, but loss of inner hair cells occurs when pillars are damaged (Bohne, 1976a). There are also physiological (Dallos et al., 1982), biochemical and metabolic differences (Vosteen, 1961; Thalmann et al., 1970; Lim and Melnick, 1971) between inner and outer hair cells which may explain outer hair cell vulnerability. This susceptibility may be an inherent property of the outer hair cell biochemistry (Saunders et al., 198513) since there is a relation between the pathology seen with noise exposures and the vulnerability of outer hair cells to ototoxic drugs. The issue is not purely biochemical or metabolic however because in animals that have had their metabolism stressed during ischemia, inner rather than outer hair cells are damaged first (Perlman et al., 1959; Jordan et al., 1973a; Bohne, 1976b). Moreover, the increased susceptibility of outer hair cells to noise trauma may also be a function of the stimulus rather than a function of the type of hair cell. In the rabbit, pure tone lesions cause primarily outer hair cell loss (Engstriim and Borg, 7981). but exposure to broad-band noise produces mainly inner hair cell loss (EngstrGm and Borg, 1983). This type of damage is independent of the presence or absence of outer hair cells (Borg and EngstrGm, 1983). Outer huir eel& uf the base are more se~s~ti~je to damage than outer hair ceiis at the apex Again. this pattern of damage to outer hair cells

may reflect structural and metabolic differences. The outer hair cells at the base may be more vulnerable because the pillar cells have a different susceptibility to noise exposure depending on their location within the organ of Corti (Bohne, 1976a). In the base, the loss of pillars and the loss of outer hair cells are parallel. Toward the apex, pillars remain until there is significant outer hair cell loss, so there may be more protection for apical outer hair cells for longer periods of time. There are also metabolic considerations. Sensory cells may differ along the length of the cochlea. There are longitudinal gradients along the length of the sensory epithelium with respect to glycogen. phosphocreatine, aspartate (Thalmann, 1976), carbonic anhydrase (Erulkar and Maren, 1961), and endolymphatic ion concentrations, osmolality and endolymphatic potential (Kuijpers and Bonting. 1970; reviewed in Sterkers et al., 1984). Support for differences in vulnerability based on metabolism has come from experiments with interrupted exposures to noise. When noise periods are kept constant and rest intervals are varied, there are longitudinal gradients with respect to the effect of rest on the magnitude of cochlear damage. Once injured, the cells in the basal turn require a longer rest period for recovery from the temporary effects of exposure than do those at the apex (Bohne et al.. 1985). Differential damage to outer hair ceN rows Recently the trend has been to focus on the vulnerability of the first row of outer hair cells after noise trauma, regardless of the type of noise exposure used (Hunter-Duvar et al., 1982). There are in fact many studies using continuous noise where the first row of hair cells is consistently damaged (Hunter-Duvar, 1977; Liberman and Beil, 1979; Robertson and Johnstone, 1980; Robertson et al.. 1980b). But there are some exceptions to this observation where the third row of outer hair cells may be the most susceptible (Beagley, 1965a; Moody et al., 1978; Stebbins et al., 1979), especially at the apex (Stockwell et al., 1969). That the order of outer hair cell vulnerability may depend on the stimulus rather than be inherent to the particular row of hair cells is suggested by the results after using impulse and impact noise trauma. While continuous noise produces first row

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outer hair cell lesions, exposure to impulse noise (high intensity, short duration, fast rise time) produces mainly third row outer hair cell damage (Nilsson et al., 1982) and exposure to impact noise (high intensity, short duration but with slower rise time than impulse noise) causes both first and third row outer hair cell damage (Lim et al., 1982). Further, when the cochlea is damaged by opening, to produce purely mechanical lesions, the third row of outer hair cells is the most vulnerable (Cody et al., 1980). Moreover, as a result of aging, the third row of outer hair cells shows the most damage (Bredberg, 1968; Dayal and Barek, 1975; Coleman, 1976; Ehret, 1979; Keithley and Feldman, 1982; Bhattacharyya and Dayal, 1985). Since different stimuli differentially affect outer hair cell rows, the mechanism of damage to these rows may be different. It has been suggested that when the third row of outer hair cells is damaged, this correlates with the fact that the third row of outer hair cells may be more affected by the vibration of the basilar membrane which begins at the Hensen cells and passes inwards and decreases in amplitude toward the modiolus (Btkesy, 1960). One may also expect that if the stereocilia are rigidly coupled to the tectorial membrane, that they would be exposed to tremendous stress. The stereocilia of third row outer hair cells are longer than the stereocilia of first row outer hair cells (see Lim, 1980) and may be more tightly coupled to the tectorial membrane. In the case of third row damage, increased damage may occur to these longer stereocilia because of the increased mechanical trauma. For other types of exposures, when first row outer hair cells are damaged first, the insertion of the stereocilia into the tectorial membrane may serve a protective function to hold the third row outer hair cell stereocilia in position and prevent mechanical breakage, or reduce the opportunities for contact between adjacent stereocilia reducing the opportunity for fusion. Since the first row of outer hair cells have the shortest stereocilia of the three rows, they may be much less firmly anchored in the tectorial membrane and they may be more prone to damage (Liberman and Beil, 1979). Also since first row outer hair cell stereocilia are stiffer than third row outer hair cell stereocilia (Strelioff and Flock, 1984) they may be more brittle. The

effect of efferent nerve activity on the structure and mechanical properties of only the first row of outer hair cells may also play a role in differential susceptibility (Liberman and Simmons, 1985). What noise damage tells us about the innervation of the cochlea Outer hair cell damage produced by noise affects thresholds and frequency selectivity of eighth nerve fibers, presumably by altering the micromechanical properties of the cochlea responsible for inner hair cell stimulus. The 95% of the afferent fibers that project to the cochlear nucleus appear to be responsible for most aspects of the perception of sound. The role of the afferent fibers that innervate outer hair cells is less clear. The fibers have been mapped using horseradish peroxidase labeling and in the adult cat they innervate predominantly third row outer hair cells (Liberman and Simmons, 1985). If the function of the fibers is sensory, then it is of interest that they innervate the cells which undergo the most motion during basilar membrane displacement. The central projections of these fine fibers have been mapped after noise trauma, when outer hair cell loss has been correlated with degeneration of fine and medium fibers projecting to the dorsal cochlear nucleus and to a lesser extent to the ventral cochlear nucleus (Morest and Bohne, 1983). Transneuronal preterminal degeneration has been noted in the pathways ascending to the superior olivary complex, an area where the cell bodies of the efferent fibers to the cochlea are located. The role of the efferents in cochlear function has not been proven, but it is known that electrical stimulation of the efferent fibers which end on outer hair cells effectively decreases the stimulus to inner hair cells (Brown et al., 1983). It is known that noise activates the efferent system and increases glucose uptake in the efferent fibers under outer hair cells (Ryan and Sharp, 1982) and that when the efferent system is activated by contralateral noise stimulation, acoustic damage to the cochlea is reduced (Cody and Johnstone, 1982). If the purpose of the efferents is to decrease input to inner hair cells, the mechanics of basilar membrane movement may be influenced most through the first row of outer hair cells. Activation of efferents shifts damage from re-

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gions that may undergo maximum displacement (OHC-3) to a region that is closer to the pillar supporting cells and should be better protected (OHC-1). Efferents may influence mechanics by changing the shape of the outer hair cells by modulating tension development and cell length. The effects of efferent activation on shortening or prevention of shortening of predominantly first row outer hair cells should be considered when predicting mechanical changes at the reticular lamina. Efferents may influence mechanics at the apical surface of the hair cell by modulating the stiffness of the stereocilia through ionic changes within the hair cell body. In this regard the first row outer hair cells are initially the stiffest (Strelioff and Flock, 1984). The effect of such changes to first row outer hair cell stereocilia may alter coupling of these stereocilia to the tectorial membrane and fluid motion. both of which would affect inner hair cell stimulation. Overstimulation by mechanical means has been a powerful tool for looking at various aspects of cochlear function. Further experiments where specific areas of the inner ear have been damaged may give us further clues to structural and functional interactions within the cochlea. References Ades. W.W., Trahiotis, C., Kokko-Cunningham and Averbuch, A. (1974): Comparison of hearing thresholds and morphological changes in the chinchilla after exposure to 4 kHz tones. Acta Otolaryngol. 78, 192-202. Angelborg, C., Hultcrantz, E. and Beausang-Linder, M (1979): The cochlear blood flow in relation to noise and cervical sympath~tomy. Adv. Oto-Gino-La~ngol. 25. 41-48. Axelsson, A. and Vertes, D. (1982): Histological finding in cochlear vessels after noise. In: New Perspectives on Noise-Induced Hearing Loss, pp. 49-67. Editors: R.P. Hamernik, D. Henderson and R. Salvi. Raven Press, New York.

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