Biomedical subjects

Alfred L Nuttall

Publications and source records attributed to Alfred L Nuttall.

27 records · Page 2Linked to original sources

PubMed2003

Altered expression of inducible nitric oxide synthase (iNOS) in the cochlea.

Using immunohistochemistry and Western blot, the expression of inducible nitric oxide synthase (iNOS) in the lateral wall and organ of Corti was examined in normal (unstimulated) and stimulated mice and guinea pigs. The stimuli were: (1). injection of bacterial lipopolysaccharide (LPS, 5 mg/ml) into the middle ear through the tympanic membrane and (2). exposure to a 110 dB SPL (A-weighted) broadband noise, 3 h/day, for three consecutive days. For the unstimulated condition, weak iNOS expression was found in the vascular endothelium, marginal cells, nerve fibers, stereocilia of hair cells and Hensen's cells of the organ of Corti. More intense iNOS fluorescence signals were observed in cochlear tissues (particularly in hair cells and stria vascularis marginal cells) in animals exposed to loud sound or treated with LPS. Although the precise roles of iNOS expression in normal cochlear function have yet to be determined, enhanced iNOS expression following noise exposure and LPS suggests its participation in cochlear pathophysiology, including noise- and inflammatory factor-induced hearing loss.

Acoustic Stimulation↗

PubMed2003

The sources of electrically evoked otoacoustic emissions.

It has been hypothesized that electrically evoked otoacoustic emissions (EEOAEs) are generated at a site on the basilar membrane near the stimulating electrode. From this original site, the energy propagates towards the oval window, giving rise to the short time delay component (SDC) of EEOAEs. The energy also propagates towards its characteristic frequency (CF) location, and the emission reflected from the CF location forms a long time delay component (LDC). This hypothesis is directly tested in this study by using an acoustical swept tone to modulate the EEOAEs generated by alternating electric current delivered to the round window niche in gerbils. An acoustical tone with a high sound pressure level or a small frequency separation from the EEOAE frequency induced a strong suppression of the EEOAE LDC, but no obvious suppression of the SDC. When the electrical current frequency was fixed, the swept acoustic tone induced a slight suppression, an enhanced peak, and a strong suppression of EEOAEs as the acoustic frequency was swept from the low to high frequency. These data indicate that the electrical current induced cochlear partition vibration near the stimulating electrode. One part of this energy propagates directly to the ear canal, forming the SDC, and the other part propagates to its CF place and is reflected from there to the ear canal, forming the LDC.

Acoustic Stimulation↗

PubMed2003

Effect of current stimulus on in vivo cochlear mechanics.

In this paper, the influence of direct current stimulation on the acoustic impulse response of the basilar membrane (BM) is studied. A positive current applied in the scala vestibuli relative to a ground electrode in the scala tympani is found to enhance gain and increase the best frequency at a given location on the BM. An opposite effect is found for a negative current. Also, the amplitude of low-frequency cochlear microphonic at high sound levels is found to change with the concurrent application of direct current stimulus. BM vibrations in response to pure tone acoustic excitation are found to possess harmonics whose levels relative to the fundamental increase with the application of positive current and decrease with the application of negative current. A model for outer hair cell activity that couples changes in length and stiffness to transmembrane potential is used to interpret the results of these experiments and others in the literature. The importance of the in vivo mechanical and electrical loading is emphasized. Simulation results show the somewhat paradoxical finding that for outer hair cells under tension, hyperpolarization causes shortening of the cell length due to the dominance of voltage dependent stiffness changes.

Acoustic Stimulation↗

PubMed2003

Basilar-membrane responses to multicomponent (Schroeder-phase) signals: understanding intensity effects.

Harmonic complexes comprised of the same spectral components in either positive-Schroeder (+Schr) or negative-Schroeder (-Schr) phase [see Schroeder, IEEE Trans. Inf. Theory 16, 85-89 (1970)] have identical long-term spectra and similar waveform envelopes. However, localized patterns of basilar-membrane (BM) excitation can be quite different in response to these two stimuli. Measurements in chinchillas showed more modulated (peakier) BM excitation for +Schr than -Schr complexes [Recio and Rhode, J. Acoust. Soc. Am. 108, 2281-2298 (2000)]. In the current study, laser velocimetry was used to examine BM responses at a location tuned to approximately 17 kHz in the basal turn of the guinea-pig cochlea, for +Schr and -Schr complexes with a 203-Hz fundamental frequency and including 101 equal-amplitude components from 2031 to 22,344 Hz. At 35-dB SPL, +Schr response waveforms showed greater amplitude modulation than -Schr responses. With increasing stimulation level, internal modulation decreased for both complexes. To understand the observed phenomena quantitatively, responses were predicted on the basis of a linearized model of the cochlea. Prediction was based on an "indirect impulse response" measured in the same animal. Response waveforms for Schroeder-phase signals were accurately predicted, provided that the level of the indirect impulse used in prediction closely matched the level of the Schroeder-phase stimulus. This result confirms that the underlying model, which originally was developed for noise stimuli, is valid for stimuli that produce completely different response waveforms. Moreover, it justifies explanation of cochlear filtering (i.e., differential treatment of different frequencies) in terms of a linear system.

Animals↗

PubMed2002

The electrochemical and fluorescence detection of nitric oxide in the cochlea and its increase following loud sound.

A nitric oxide (NO)-selective sensor (tip diameter 30 microm) was inserted into the perilymph of the basal turn of the guinea pig cochlea. The basal level and stimulation-induced changes of NO were measured. The mean (+/-S.E.M.) basal level of NO was 273+/-42.9 nM. Following perilymphatic perfusion of the artificial perilymph containing NO synthase (NOS) substrate L-arginine (100 microM) combined with cofactor (6R)-5,6,7,8-tetrahydrobiopterin dihydrochloride (100 microM), a rapid and significant increase of NO to a mean concentration of 392+/-32.3 nM (P < 0.01, n = 10) was recorded. In contrast, a significant decrease of mean NO concentration to 180+/-32.7 nM (P < 0.01, n = 10) was observed following the perfusion of the NOS-inhibiting agent N(G)-nitro-L-arginine methyl ester (100 microM). No change in the NO concentration was found following the perfusion of either artificial perilymph or N(G)-monomethyl-D-arginine (100 microM) solution employed as controls. Broadband noise exposure (3 h/day at 120 dBA SPL) for three consecutive days produced an increase in NO concentration to 618+/-60.7 nM (P < 0.05, n = 10) in the perilymph. In addition, by using specific dyes for NO, 4,5-diaminofluoresceine diacetate and for the reactive oxygen species (ROS), dihydrorhodamine 1,2,3, the distribution of NO in the whole mounts of the organ of Corti and the production of ROS in vivo in the organ of Corti were investigated in both control (n = 5) and noise-exposed (n = 5) animals. The more intense NO and ROS fluorescence was observed in both the inner and outer hair cells in the noise-exposed groups. It is proposed that both the basal level and the increase in NO concentration following the addition of substrate (L-arginine) are produced by the constitutive NOS while the elevated NO and ROS following noise exposure indicate that NO may be involved in noise-induced hearing loss.

Animals↗

PubMed2002

Nitric oxide induces hyperpolarization by opening ATP-sensitive K(+) channels in guinea pig spiral modiolar artery.

Nitric oxide (NO) hyperpolarizes vascular smooth muscle cells and dilates blood vessels of various beds, but little is known on cochlear vasculatures. Using in vitro preparations of the spiral modiolar artery (SMA), intracellular electrical recording and labeling techniques, we found that the NO donor DPTA-NONOate (10 microM) caused a hyperpolarization of approximately 9 mV in all the cells that had a low resting potential (RP) level near -40 mV. The hyperpolarization amplitude was concentration-dependent, with a 50% effect concentration (EC(50)) of 1 microM. The responses occur in both smooth muscle and endothelial cells, neither of which was blocked by 18beta-glycyrrhetinic acid. The induced hyperpolarization was completely blocked by glipizide, but not by charybdotoxin, apamin, barium, 4-aminopyridine or tetraethylammonium. The hyperpolarizing responses were imitated by pinacidil (EC(50)=30 microM). The pinacidil-induced response was also blocked by glipizide but not by the other K(+) channel blockers mentioned above. Both DPTA-NONOate and pinacidil had little membrane potential effect on cells that had a high RP level near -75 mV. However, when the high RP cells were depolarized to a level beyond -45 mV by barium, both DPTA-NONOate and pinacidil hyperpolarized these cells not differently from those that initially had a low RP. It is concluded that NO hyperpolarizes the SMA primarily by activating K(ATP) channels in both muscle and endothelial cells.

Adenosine Triphosphate↗

PubMed2002

The demonstration of nitric oxide in cochlear blood vessels in vivo and in vitro: the role of endothelial nitric oxide in venular permeability.

The objectives of the current study were to investigate the distribution and production of NO in cochlear blood vessels, and to assess whether the inhibition of basal NO production leads to vascular protein leakage of the cochlear microvasculature. Using the fluorescent dye 4,5-diaminofluorescein diacetate, NO was detected, both in vitro and in vivo, in the endothelial cells of various cochlear blood vessels, including the spiral modiolar artery, the vessel of the basilar membrane and the vessels of the spiral osseous lamina. Vessel leakage was assessed using intravital fluorescence microscopy following systemic infusion of fluorescein isothiocyanate-labeled bovine albumin. Local perfusion of the cochlear basal turn with either Ringer's solution or Ringer's containing an inactive nitric oxide synthase inhibitor (100 microM) produced minimal protein leakage. Perfusion with the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (100 microM) produced significantly enhanced vascular protein leakage. The findings demonstrate the presence of endothelial NO in the cochlear blood vessels and suggest that NO protects cochlear venules against excessive vascular leakage.

Animals↗

PubMed2002

The mechanical waveform of the basilar membrane. IV. Tone and noise stimuli.

Analysis of mechanical cochlear responses to wide bands of random noise clarifies many effects of cochlear nonlinearity. The previous paper [de Boer and Nuttall, J. Acoust. Soc. Am. 107, 1497-1507 (2000)] illustrates how closely results of computations in a nonlinear cochlear model agree with responses from physiological experiments. In the present paper results for tone stimuli are reported. It was found that the measured frequency response for pure tones differs little from the frequency response associated with a noise signal. For strong stimuli, well into the nonlinear region, tones have to be presented at a specific level with respect to the noise for this to be true. In this report the nonlinear cochlear model originally developed for noise analysis was modified to accommodate pure tones. For this purpose the efficiency with which outer hair cells modify the basilar-membrane response was made into a function of cochlear location based on local excitation. For each experiment, the modified model is able to account for the experimental findings, within 1 or 2 dB. Therefore, the model explains why the type of filtering that tones undergo in the cochlea is essentially the same as that for noise signals (provided the tones are presented at the appropriate level).

Acoustic Stimulation↗

PubMedDate not supplied

In vivo micromechanical measurements of the organ of Corti in the basal cochlear turn.

Cochlear mechanical measurements of organ of Corti motion are generally accomplished in the apical or basal turn as in vivo or in vitro studies. In the apex it is possible to observe and measure tectorial membrane vibration as well as vibrations of structures such as the reticular lamina or the basilar membrane (BM). However, compared to the basal turn, cochlear amplification and nonlinearity are not strong in the apex. Basal turn studies have typically been limited to point location measurements of the BM but improved technology for laser interferometry is now making possible the spatial mapping of BM motion. The 'complexity' of BM motion in the radial direction (particularly the phase variation) is important to new models of cochlear wave amplification. In future work it may be possible to learn about vibration of structures within the organ of Corti.

Animals↗