Biomedical subjects

Alfred L Nuttall

Publications and source records attributed to Alfred L Nuttall.

At least 19 recordsLinked to original sources

PubMed2006

Expression of adhesion molecular proteins in the cochlear lateral wall of normal and PARP-1 mutant mice.

Sound can damage peripheral cochlear function through a number of mechanisms, and emerging evidence suggests that inflammation may be one of them. Using immunohistochemistry and poly (ADP-ribose) polymerase-1 (PARP-1) mutant mice, we tested whether PARP-1 contributes to loud-sound induced cochlear lateral wall damage by triggering inflammatory effects, including upregulating intercellular adhesion molecule-1 (ICAM-1), P-selectin and platelet-endothelial cell-adhesion molecule-1 (PECAM-1). In control conditions, we found that there was no detectable poly-ADP-ribose (PAR) in the marginal cells and microvessels. ICAM-1 was expressed only at low levels in the vessels of the stria vascularis and the spiral ligament. P-selectin and PECAM-1 were barely detected and only in the vessels of the spiral ligament. Following loud-sound exposure, PAR was detected in numbers of marginal cells and some vessels of the spiral ligament. Also, an elevated expression of ICAM-1 was demonstrated in some vessels of the stria vascularis and spiral ligament. Increased expression of P-selectin and PECAM-1 were mainly located in the vessels of the spiral ligament, while increased populations of non-migrated and migrated leukocytes were observed in the area of the spiral ligament. However, neither increased expression of adhesion proteins nor increased population of leukocytes, were observed in the PARP-1 knockout mouse. We thus conclude that loud-sound stress activates the expression of adhesion molecular proteins in the lateral wall and that PARP-1 modulates inflammation-linked protein expression and leukocyte migration.

Animals↗

PubMed2006

Chlorpromazine alters cochlear mechanics and amplification: in vivo evidence for a role of stiffness modulation in the organ of corti.

Although prestin-mediated outer hair cell (OHC) electromotility provides mechanical force for sound amplification in the mammalian cochlea, proper OHC stiffness is required to maintain normal electromotility and to transmit mechanical force to the basilar membrane (BM). To investigate the in vivo role of OHC stiffness in cochlear amplification, chlorpromazine (CPZ), an antipsychotic drug that alters OHC lateral wall biophysics, was infused into the cochleae in living guinea pigs. The effects of CPZ on cochlear amplification and OHC electromotility were observed by measuring the acoustically and electrically evoked BM motions. CPZ significantly reduced cochlear amplification as measured by a decline of the acoustically evoked BM motion near the best frequency (BF) accompanied by a loss of nonlinearity and broadened tuning. It also substantially reduced electrically evoked BM vibration near the BF and at frequencies above BF (< or =80 kHz). The high-frequency notch (near 50 kHz) in the electrically evoked BM response shifted toward higher frequency in a CPZ concentration-dependent manner with a corresponding phase change. In contrast, salicylate resulted in a shift in this notch toward lower frequency. These results indicate that CPZ reduces OHC-mediated cochlear amplification probably via its effects on the mechanics of the OHC plasma membrane rather than via a direct effect on the OHC motor, prestin. Through modeling, we propose that with a combined OHC somatic and hair bundle forcing, the upward-shift of the approximately 50-kHz notch in the electrically-evoked BM motion may indicate stiffness increase of the OHCs that is responsible for the reduced cochlear amplification.

Acoustic Stimulation↗

PubMed2006

Low coherence interferometry of the cochlear partition.

Interferometric measurement of the vibration of the organ of Corti in the isolated guinea pig cochlea was conducted using low-coherence light (1310+/-47 nm wavelength) from a superluminescent diode. The short coherence length of the light source localized measurements along the axial direction to within a approximately 10-microm window (in tissue), even when using a low numerical-aperture lens. The ability to accomplish this is important because measurement of the vibration of the basal-turn organ of Corti is generally done via a small hole in the bone of the cochlea, which effectively limits the numerical aperture. The axial localization, combined with the inherent sensitivity of the method, allowed distinct measurements of the basilar membrane (BM) and the putative reticular lamina (RL) vibration using only the native tissue reflectance, that is without requiring the use of reflective particles. The system was first operated in a scanning mode as an optical coherence tomography (OCT) system to yield an image of the organ of Corti. The reflectance of intensity from the BM and RL was 8x10(-5) and 8x10(-6), respectively. The internal structure between the BM and RL presented a variable reflectivity of about 10(-7). A mirror would define a reflectance of 1.00. Then the instrument was operated as a homodyne interferometer to measure the displacement of either the BM or RL. Vibration at 16 kHz was induced by a piezoelectric actuator, causing whole movement of a dissected cochlea. After calibration of the system, we demonstrated clear measurement of mechanically driven vibration for both the BM and RL of 0.30 nm above a noise floor equivalent to 0.03 nm. OCT interferometry, when adapted for in vivo organ of Corti measurements, appears suitable to determine the micromechanical vibration of cells and tissue elements of the organ.

Animals↗

PubMed2006

Group delay of acoustic emissions in the ear.

It is commonly accepted that the cochlea emits sound by a backward traveling wave along the cochlear partition. This belief is mainly based on an observation that the group delay of the otoacoustic emission measured in the ear canal is twice as long as the forward delay. In this study, the otoacoustic emission was measured in the gerbil under anesthesia not only in the ear canal but also at the stapes, eliminating measurement errors arising from unknown external- and middle-ear delays. The emission group delay measured at the stapes was compared with the group delay of basilar membrane vibration at the putative emission-generation site, the forward delay. The results show that the total intracochlear delay of the emission is equal to or smaller than the forward delay. For emissions with an f2/f1 ratio <1.2, the data indicate that the reverse propagation of the emission from its generation site to the stapes is much faster than a forward traveling wave to the f2 location. In addition, that the round-trip delays are smaller than the forward delay implies a basal shift of the emission generation site, likely explained by the basal shift of primary-tone response peaks with increasing intensity. However, for emissions with an f1 << f2, the data cannot distinguish backward traveling waves from compression waves because of a very small f1 delay at the f2 site.

Algorithms↗

PubMed2006

Control of mammalian cochlear amplification by chloride anions.

Chloride ions have been hypothesized to interact with the membrane outer hair cell (OHC) motor protein, prestin on its intracellular domain to confer voltage sensitivity (Oliver et al., 2001). Thus, we hypothesized previously that transmembrane chloride movements via the lateral membrane conductance of the cell, GmetL, could serve to underlie cochlear amplification in the mammal. Here, we report on experimental manipulations of chloride-dependent OHC motor activity in vitro and in vivo. In vitro, we focused on the signature electrical characteristic of the motor, the nonlinear capacitance of the cell. Using the well known ototoxicant, salicylate, which competes with the putative anion binding or interaction site of prestin to assess level-dependent interactions of chloride with prestin, we determined that the resting level of chloride in OHCs is near or below 10 mm, whereas perilymphatic levels are known to be approximately 140 mm. With this observation, we sought to determine the effects of perilymphatic chloride level manipulations of basilar membrane amplification in the living guinea pig. By either direct basolateral perfusion of the OHC with altered chloride content perilymphatic solutions or by the use of tributyltin, a chloride ionophore, we found alterations in OHC electromechanical activity and cochlear amplification, which are fully reversible. Because these anionic manipulations do not impact on the cation selective stereociliary process or the endolymphatic potential, our data lend additional support to the argument that prestin activity dominates the process of mammalian cochlear amplification.

Animals↗

PubMed2006

Spontaneous basilar-membrane oscillation (SBMO) and coherent reflection.

In a previous report (in JARO) we have described a relatively high-frequency (15 kHz) spontaneous oscillation of the basilar membrane (SBMO) in a guinea pig ear; this oscillation was accompanied by a spontaneous otoacoustic emission (SOAE) at the same frequency. During the spontaneous oscillation and after it had subsided, the mechanical frequency response of the basilar membrane was measured by way of a wide-band random-noise stimulus, and it showed a number of spectral peaks, one of which having the frequency of the original oscillation. This pattern of peaks cannot be explained by assuming a single place of reflection in the cochlea. In this paper the process of 'coherent reflection' is artificially evoked in a three-dimensional model of the cochlea by imposing random place-fixed irregularities to the basilar-membrane impedance. It is shown that in the model a series of peaks arises in the frequency spectrum of the basilar-membrane response which phenomenon resembles the one found in the experimental animal. It is also shown that these peaks are actually due to superposition of the primary wave and a wave resulting from 'coherent reflection' which is reflected at the stapes. When the intensity of the acoustic stimulus signal is increased, the relative sizes of these peaks in the simulation diminish in about the same way as in the experiment. It is concluded that coherent reflection most likely is the cause of the 'extra peaks', and that this concept can also explain the observed level dependence of these peaks. The findings of this study lead to a minor refinement regarding the actual requirements for coherent reflection to arise.

Acoustic Stimulation↗

PubMed2006

Cochlear compression wave: an implication of the Allen-Fahey experiment.

In order to measure the gain of the cochlear amplifier, de Boer and co-workers recently extended the Allen-Fahey experiment by measuring otoacoustic emissions and basilar membrane vibration [J. Acoust. Soc. Am. 117, 1260-1266 (2005)]. Although this new experiment overcame the limitation of the original Allen-Fahey experiment for using a low-frequency ratio, it confirmed the previous finding that there is no detectable cochlear amplification. This result was attributed to destructive interference of the otoacoustic emission over its generation site. The present letter provides an alternative interpretation of the results of the Allen-Fahey experiment based on the cochlear fluid compression-wave theory.

Acoustic Impedance Tests↗

PubMed2005

AIF and endoG translocation in noise exposure induced hair cell death.

Activation of caspases is a key element in the apoptotic process. However, mitochondria also play an important role via the release of proapoptotic proteins. This study investigated the roles of mitochondria-related apoptosis inducing factor (AIF) and endonuclease G (endoG), mitochondrion-specific nucleases, as well as caspase-3, an important mediator of apoptosis, in noise exposure induced hair cell death. Guinea pigs were exposed for 4h/day to broadband noise at 122 dB SPL for 2 days. After the noise exposure, the cochleae were examined for the activity of caspase-3 with carboxyfluorescein-labeled fluoromethyl ketone (FMK)-peptide inhibitors. The cochleae were further examined for AIF and endoG translocation from the mitochondria by immunohistochemistry. Noise exposure triggered activation of caspase-3 in apoptotic hair cells. In the normal organ of Corti, AIF and endoG were co-localized to the mitochondria. After noise exposure, AIF translocated into the nuclei of apoptotic and necrotic hair cells. The translocation of endoG from mitochondria into the nucleus was also found in apoptotic OHCs. These findings indicate that mitochondria-released proapoptotic proteins, AIF and endoG, are important factors in a noise-induced hair cell death pathway.

Active Transport, Cell Nucleus↗

PubMed2005

Electrical coupling and release of K+ from endothelial cells co-mediate ACh-induced smooth muscle hyperpolarization in guinea-pig inner ear artery.

The physiological basis of ACh-elicited hyperpolarization in guinea-pig in vitro cochlear spiral modiolar artery (SMA) was investigated by intracellular recording combined with dye labelling of recorded cells and immunocytochemistry. We found the following. (1) The ACh-hyperpolarization was prominent only in cells that had a low resting potential (less negative than -60 mV). ACh-hyperpolarization was reversibly blocked by 4-DAMP, charybdotoxin or BAPTA-AM, but not by N(omega)-nitro-L-arginine methyl ester, glipizide, indomethacin or 17-octadecynoic acid. (2) Ba(2)(+) (100 microm) and ouabain (1 microm) each attenuated ACh-hyperpolarization by approximately 30% in smooth muscle cells (SMCs) but had only slight or no inhibition in endothelial cells (ECs). A combination of Ba(2)(+) and 18beta-glycyrrhetinic acid near completely blocked the ACh-hyperpolarization in SMCs. (3) High K(+) (10 mm) induced a smaller hyperpolarization in ECs than in SMCs, with an amplitude ratio of 0.49 : 1. Ba(2)(+) blocked the K(+)-induced hyperpolarization by approximately 85% in both cell types, whereas ouabain inhibited K(+)-hyperpolarization differently in SMCs (19%) and ECs (35%) and increased input resistance. 18beta-Glycyrrhetinic acid blocked the high K(+)-hyperpolarization in ECs only. (4) Weak myoendothelial dye coupling was detected by confocal microscopy in cells recorded with a propidium iodide-containing electrode for longer than 30 min. A sparse plexus of choline acetyltransferase-immunoreactive (ChAT) fibres was observed around the SMA and its up-stream arteries. (5) Evoked excitatory junction potentials (EJP) were partially blocked by 4-DAMP in half of the cells tested. We conclude that ACh-induced hyperpolarization originates from ECs via activation of Ca(2)(+)-activated potassium channels, and is independent of the release of NO, cyclo-oxygenase or cytochrome P450 products. ACh-induced hyperpolarization in smooth muscle cells involves two mechanisms: (a) electrical spread of the hyperpolarization from the endothelium, and (b) activation of inward rectifier K(+) channels (K(ir)) and Na(+)-K(+) pump current by elevated interstitial K(+) released from the endothelial cells, these being responsible for about 60% and 40% of the hyperpolarization, respectively. The role ratio of K(ir) and pump current activation is at 8 : 1 or less.

Acetylcholine↗

PubMed2005

Na+ influx triggers bleb formation on inner hair cells.

Large blebs form rapidly on apical membranes of sensory inner hair cells (IHCs) when the organ of Corti is freshly isolated from adult guinea pigs. Bleb formation had two distinguishable phases. Initially, we identified small particles labeled with fluorescent annexin V; these rapidly coalesced into larger aggregates. After particle aggregation, a single membrane bleb emerged from cuticular plate at the vestigial kinocilium location, eventually reaching approximately 10 microm maximum spherical diameter; blebs this size often detached from IHCs. Development of blebs was associated with elevated concentration of intracellular Na(+); blocking Na(+) influx through mechanotransduction and ATP channels in the apical pole of IHCs or by replacement of Na(+) with N-methyl-D-glucamine prevented Na(+) loading and bleb formation. Depletion of intracellular ATP, blocking cAMP synthesis, inhibition of vesicular transport with brefeldin A, or inhibition of phosphatidylinositol 3-kinase with 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one (LY-294002) significantly reduced bleb formation in the presence of a Na(+) load. Neither the mechanism of blebbing nor the size growth of the IHC blebs was associated with cellular apoptosis or necrosis. Bleb formation was not significantly reduced by disassembling microtubules or decreasing intracellular hydrostatic pressure. Moreover, no polymerized actin was observed in the lumen of blebs. We conclude that IHC bleb formation differs from classic blebbing mechanisms and that IHC blebs arise from imbalance of endocytosis and exocytosis in the apical plasma membrane, linked to Na(+) loading that occurs in vitro.

Actins↗

PubMed2005

Spatial distribution of electrically induced high frequency vibration on basilar membrane.

We reported that the electrically evoked basilar membrane (BM) vibration at frequencies above the best frequency (BF) showed a lowest BM velocity magnitude, called a "dip", in the velocity-frequency spectra, indicating a cancellation. In the present study, we measured the high frequency BM motion as functions of the longitudinal and radial locations. Measurements were taken at three longitudinal locations in the first turn and the hook region: 14.9, 15.8 and 16.8 mm from the apex, corresponding to the BFs of 17, 21.3 and 28.0 kHz calculated from Greenwood [J. Acoust. Soc. Am. 87, 2592], and at different radial locations across the width of the BM. It was found that the dip frequency (DF) varied with the longitudinal and radial locations. In the longitudinal direction, the average value of the DF was 49.6, 55.6 and 72.8 kHz, respectively. Thus, the longitudinal distribution of the high frequency BM vibration was correlated with the BF. In the radial direction, there was consistent variation of the response spectrum such that the dip was mainly evident in the pectinate zone of the BM. These results imply that the high frequency BM motion is related to mechanical properties of the cochlear partition, including the outer hair cells (OHCs) themselves. Data also indicate different vibration modes across the width of the organ of Corti.

Acoustic Stimulation↗

PubMed2005

The Allen-Fahey experiment extended.

An ingenious experiment has been performed by Allen and Fahey [J. Acoust. Soc. Am. 92, 178-188 (1992)], in which they attempted to estimate the gain of the cochlear amplifier by comparing responses to the 2 f1-f2 distortion product (DP) in the outer ear canal (otoacoustic emissions) and from an auditory-nerve fiber. Results were essentially negative: no evidence of cochlear amplification was found in that experiment. A variation of that experiment is reported here, where DP responses in the outer ear canal are compared with mechanical responses of the basilar membrane. This variation does not suffer from the major limitation in the original experiment in the choice of possible frequency ratios. Results confirm and extend those of Allen and Fahey entirely. Apparently, the gain of the cochlear amplifier cannot be measured in this way. It is argued that the retrograde wave going to the stapes is most likely reduced in magnitude by wave interference when the two primary frequencies approach each other. Such a reduction does not take place in the forward-going wave to the location tuned to the DP frequency. This explanation is illustrated on the basis of results of earlier experiments on the movements of the basilar membrane.

Animals↗

PubMed2004

Cochlear delays measured with amplitude-modulated tone-burst-evoked OAEs.

Delay times in the mammalian cochlea, whether from measurement of basilar membrane (BM) vibration or otoacoustic emissions (OAEs) have, to date, been largely based on phase-gradient estimates from steady-state responses. Here we report cochlear delays measured directly in the time domain from OAEs evoked by amplitude-modulated tone-burst (AMTB) stimuli. Measurement using OAEs provides a non-invasive estimate of cochlear delay but is confounded by the complexity of generation of such OAEs. At low to moderate stimulus levels, and provided that the stimulus frequency range does not include a region of the cochlea where there is a large change in effective reflectance, AMTB stimuli evoke an OAE with an envelope shape that is similar to the stimulus and allow a direct calculation of cochlear group delay. Such delays are commensurate with BM estimates of delay, estimates of cochlear delay inferred from neural recordings, and previous OAE measures of delay in the guinea pig. However, a nonlinear distortion mechanism, variation in effective reflectance, and intermodulation distortion products generated by the nonlinear interaction in the cochlea of the carrier and sidebands of the AMTB stimulus, may all contribute to OAEs arising with envelope shapes that are not a scaled representation of the stimulus, confounding the estimation of cochlear group delay.

Acoustic Stimulation↗

PubMed2004

Basal nitric oxide production contributes to membrane potential and vasotone regulation of guinea pig in vitro spiral modiolar artery.

Nitric oxide (NO) is a potent vasodilating agent implicated in cochlear blood flow regulation. We recently demonstrated that exogenously applied NO donor DPTA-NONOate hyperpolarizes both endothelial and smooth muscle cells of in vitro spiral modiolar artery (SMA) via activation of ATP-sensitive K+ channels (K(ATP)). Also, NO was detected in the SMA cells by NO indicator dye in the in vitro basal condition. Using intracellular recording techniques, electrochemical NO-sensing measurement, and a vaso-diameter video tracking method, we investigated the basal release of NO from the in vitro SMA and its role in the vascular function. We found that (1) 300 microM L-NAME, a NO synthase inhibitor, and 3 microM glipizide caused a depolarization of approximately 4.5 and approximately 3.2 mV, respectively, in cells with a resting potential less negative than -60 mV; (2) NO sensor in the close vicinity of the SMA detected a NO concentration of approximately 50 nM that was suppressed by L-NAME and enhanced by L-arginine (1-1000 microM); (3) NO donor DPTA-NONOate (0.1-30 microM) applications produced about 8-245 nM of NO in the recording bath. These data indicate a NO concentration-hyperpolarization relation, with an EC50 of 22 nM. (4) Finally, L-NAME but not glipizide produced a 4.8% reduction in SMA diameter (approximately 50 microm) in the majority of SMAs, whereas NONOate (10 microM) always caused a dilation. Both the induced constriction and dilation were not significantly affected by 3 microM glipizide. We conclude that a significant amount of NO (> 50 nM) is tonically released from the in vitro SMA, which is above the EC50 for activation of K(ATP), and thus contributes to the membrane polarization. The basal release of NO also contributes to vasotone relaxation, but the K(ATP) activation appears to play little role in the relaxation of the in vitro SMA.

Animals↗

PubMed2004

High-frequency electromotile responses in the cochlea.

Mammalian outer hair cells (OHCs) convert electrical energy into mechanical energy. The significance of this electromotility rests in the ability of the OHCs to modulate the vibrations of the cochlear partition in vivo. While high-frequency electromotility of isolated OHCs has been demonstrated at frequencies up to 100 kHz, a similar measure of the effect of OHC electromotility on motion of the sensory epithelium has not been made in vivo. In this study, in vivo electrical stimulation of the guinea pig cochlea is found to induce a mechanical response of the basilar membrane for frequencies to at least 100 kHz, nearly twice the upper limit of hearing for the guinea pig. The perfusion of salicylate in the cochlea reversibly reduces the electromotile response, indicating that an OHC-mediated process is the key contributor.

Acoustic Stimulation↗

PubMed2003

Upregulated iNOS and oxidative damage to the cochlear stria vascularis due to noise stress.

Our previous work has revealed increased nitric oxide (NO) production in the cochlear perilymph following noise stress. However, it is not clear if the increase of NO is related to iNOS and whether NO-related oxidative stress can cause vascular tissue damage. In this study, iNOS immunoreactivity, NO production, and reactive oxygen species (ROS) in the lateral wall were examined in normal mice and compared with similar animals exposed to 120 dBA broadband noise, 3 h/day, for 2 consecutive days. In the normal animals, iNOS expression was not observed in the vascular endothelium of the stria vascularis and only weak iNOS immunoactivity was detected in the marginal cells. However, expression of iNOS in the wall of the blood vessels of stria vascularis and marginal cells was observed after loud sound stress (LSS). Relatively low levels of NO production and low ROS activity were detected in the stria vascularis in the unstimulated condition. In contrast, NO production was increased and ROS activity was elevated in the stria vascularis after LSS. These changes were attenuated by the iNOS inhibitor, GW 274150. To explore whether noise induces apoptotic processes in the stria vascularis, we examined morphological changes in endothelial- and marginal-cells. In vitro, annexin-V phosphatidylserine (PS) (to label and detect early evidence of apoptosis) was combined with propidium iodide (PI) (to probe plasma membrane integrity). PI alone was used in fixed tissues to detect later stage apoptotic cells by morphology of the nuclei. Following LSS, PS was expressed on cell surfaces of endothelial cells of blood vessels and marginal cells of the stria vascularis. Later stage apoptosis, characterized by irregular nuclei and condensation of nuclei, was also observed in these cells. The data indicate that increased iNOS expression and production of both NO and ROS following noise stress may lead to marginal cell pathology, and the dysfunction of cochlear microcirculation by inducing blood vessel wall damage.

Animals↗

PubMed2003

Vanilloid receptors in hearing: altered cochlear sensitivity by vanilloids and expression of TRPV1 in the organ of corti.

Capsaicin, the vanilloid that selectively activates vanilloid receptors (VRs) on sensory neurons for noxious perception, has been reported to increase cochlear blood flow (CBF). VR-related receptors have also been found in the inner ear. This study aims to address the question as to whether VRs exist in the organ of Corti and play a role in cochlear physiology. Capsaicin or the more potent VR agonist, resiniferatoxin (RTX), was infused into the scala tympani of guinea pig cochlea, and their effects on cochlear sensitivity were investigated. Capsaicin (20 microM) elevated the threshold of auditory nerve compound action potential and reduced the magnitude of cochlear microphonic and electrically evoked otoacoustic emissions. These effects were reversible and could be blocked by a competitive antagonist, capsazepine. Application of 2 microM RTX resulted in cochlear sensitivity alterations similar to that by capsaicin, which could also be blocked by capsazepine. A desensitization phenomenon was observed in the case of prolonged perfusion with either capsaicin or RTX. Brief increase of CBF by capsaicin was confirmed, and the endocochlear potential was not decreased. Basilar membrane velocity (BM) growth functions near the best frequency and BM tuning were altered by capsaicin. Immunohistochemistry study revealed the presence of vanilloid receptor type 1 of the transient receptor potential channel family in the hair cells and supporting cells of the organ of Corti and the spiral ganglion cells of the cochlea. The results indicate that the main action of capsaicin is on outer hair cells and suggest that VRs in the cochlea play a role in cochlear homeostasis.

Acoustic Stimulation↗

PubMed2003

Disorders of cochlear blood flow.

The cochlea is principally supplied from the inner ear artery (labyrinthine artery), which is usually a branch of the anterior inferior cerebellar artery. Cochlear blood flow is a function of cochlear perfusion pressure, which is calculated as the difference between mean arterial blood pressure and inner ear fluid pressure. Many otologic disorders such as noise-induced hearing loss, endolymphatic hydrops and presbycusis are suspected of being related to alterations in cochlear blood flow. However, the human cochlea is not easily accessible for investigation because this delicate sensory organ is hidden deep in the temporal bone. In patients with sensorineural hearing loss, magnetic resonance imaging, laser-Doppler flowmetry and ultrasonography have been used to investigate the status of cochlear blood flow. There have been many reports of hearing loss that were considered to be caused by blood flow disturbance in the cochlea. However, direct evidence of blood flow disturbance in the cochlea is still lacking in most of the cases.

Animals↗