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A L Nuttall

Publications and source records attributed to A L Nuttall.

At least 37 records · Page 2Linked to original sources
PubMed1999

Membrane properties and the excitatory junction potentials in smooth muscle cells of cochlear spiral modiolar artery in guinea pigs.

Blood circulation changes in the inner ear play an important role in many physiological and pathological conditions of hearing function. The spiral modiolar artery (SMA) is the terminal artery to the cochlea. It was surrounded with nerve fibers immunostained by an antibody for tyrosine hydroxylase. By using intracellular recording techniques on the acutely isolated SMA, membrane properties of the smooth muscle cells and the neuromuscular transmission in this preparation were investigated. With minimum tension and normal extracellular K(+) concentration (5 mM), the majority of muscle cells showed a resting potential near -80 mV and an input resistance of about 8 MOmega. V/I plot showed an inward rectification in these cells. Barium (50-500 microM) caused strong depolarization and an increase in input resistance. Transmural electrical stimulation evoked stimulation intensity-dependent depolarizations (2-31 mV) following a short latency ( approximately 20 ms). The evoked potential by a low intensity stimulus was completely blocked by 1 microM tetrodotoxin. The potential and a depolarization induced by norepinephrine (10 microM) was usually partially (40-90%) blocked by alpha-receptor antagonists prazosin and/or idazoxan with concentrations up to 1 microM. Action potentials were observed when the depolarization was more than -40 mV. It is concluded that SMA smooth muscle cells, similar to those in other brain small arteries, highly express inward rectifying potassium channels; the cells receive catecholaminergic innervation, and stimulation of the nerves elicited an excitatory junction potential that is partially mediated by adrenergic receptors.

Animals↗
PubMed1999

The "inverse problem" solved for a three-dimensional model of the cochlea. III. Brushing-up the solution method.

In two earlier papers [de Boer, J. Acoust. Soc. Am. 98, 896-903 and 904-910 (1995)] the inherent problems of the inverse-solution method in cochlear mechanics were described. The present paper shows results obtained with a more universal solution method. With the new method it is possible to construct a three-dimensional model of the cochlea producing a response that accurately simulates a measured mechanical basilar-membrane response. With earlier methods this could not be done. The inverse solution invariably yields that, with low stimulus levels, the model simulating a viable cochlea must be locally active. For the response of a dead animal a passive model is sufficient. Once more the inherent intricacies and problems of the inverse-solution method are discussed. Conservation of fluid volume leads to the concept of the "virtual stapes velocity." For best results, the input signal to the inverse-solution procedure should be acquired in the form of a "composite cross-correlation spectrum." Inverse analysis can, under certain circumstances, produce aberrant results. In this paper it is shown why the resulting impedance function is the most accurate in the region of the response peak. Therefore, it is unlikely that a passive model would exist of which the response simulates the data obtained from a healthy animal.

Acoustic Stimulation↗
PubMed1998

Influence of intense sound exposure on glutathione synthesis in the cochlea.

Previous studies have shown that depletion of endogenous glutathione (GSH) potentiates noise-induced hearing loss (NIHL), whereas replenishment of GSH attenuates NIHL (Yamasoba et al., Brain Res. 784 (1998) 82-90). Since these findings indicate an important role of GSH in protection from NIHL, we assessed the influence of intense sound exposure (broadband noise, 105 dB SPL, 5 h) on GSH and cysteine levels in the guinea pig cochlea using high performance liquid chromatography. GSH levels were significantly increased in the lateral wall 2 and 4 h post-exposure and returned to normal 6 h post-exposure. GSH levels in the sensory epithelium and modiolus did not show significant changes following noise. Cysteine levels were unchanged in any of the cochlear segments. For the cochlea as a whole, intense sound exposure did not significantly change GSH or cysteine levels throughout the 6-h measurement period post-exposure. These results indicate that GSH synthesis is markedly upregulated selectively in the lateral wall by noise exposure, presumably in response to the robust consumption of GSH, as it is utilized in scavenging reactive oxygen species.

Animals↗
PubMed1998

Role of glutathione in protection against noise-induced hearing loss.

A potential mechanism of hearing loss due to acoustic overstimulation is the generation of reactive oxygen species (ROS). ROS not removed by antioxidant defenses could be expected to cause significant damage to the sensory cells of the cochlea. We studied the influence of the antioxidant glutathione (GSH) on noise-induced hearing loss by using l-buthionine-[S,R]-sulfoximine (BSO), an inhibitor of GSH synthesis, and 2-oxothiazolidine-4-carboxylate (OTC), a cysteine prodrug, which promotes rapid restoration of GSH when GSH is acutely depleted. Pigmented female guinea pigs were exposed to broadband noise (102 dB SPL, 3 h/day, 5 days) while receiving daily injections of BSO, OTC, or saline. By weeks 2 and 3 after noise exposure, BSO-treated animals showed significantly greater threshold shifts above 12 kHz than saline-treated subjects, whereas OTC-treated animals showed significantly smaller threshold shifts at 12 kHz than controls. Histologically assessed noise-induced damage to the organ of Corti, predominantly basal turn row 1 outer hair cells, was most pronounced in BSO-treated animals. High performance liquid chromatographic analysis showed that OTC significantly increased cysteine levels, but not GSH levels, in the cochlea. These findings show that GSH inhibition increases the susceptibility of the cochlea to noise-induced damage and that replenishing GSH, presumably by enhancing availability of cysteine, attenuates noise-induced cochlear damage.

Animals↗
PubMed1998

Endolymphatic hydrops reduces retrograde labeling of trigeminal innervation to the cochlea.

This paper reports that endolymphatic hydrops causes a significant reduction of retrogradely labeled cell bodies of the ipsilateral trigeminal ganglion following application of horseradish peroxidase in the cochlea. We previously showed that the trigeminal ganglion is a source of primary sensory innervation to the cochlear blood vessels. The innervation of the cochlea from the trigeminal ganglion may provide the basis of an alternative mechanism for Ménière's syndrome (imbalance, hearing loss, tinnitus, and a sensation of fullness in the ear) for which a central neural basis has been speculated. Innervation patterns of sensory nerves from the trigeminal ganglion to the cochlear blood vessels were studied using retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Healthy and hydropic guinea pigs were unilaterally implanted with an osmotic pump and a cannula for cochlear delivery of 2% WGA-HRP or vehicle alone. In other guinea pigs the cochlea was pretreated with 100 micromol capsaicin before administering 2% WGA-HRP. Histological sections of the ipsi- and contralateral trigeminal ganglia were obtained 48 h after WGA-HRP infusion. In the hydropic guinea pig, the number of labeled nerve cell bodies observed in the anteriomedial portion of the trigeminal ganglion at the origin of the ophthalmic nerve was reduced by 70% relative to normal animals. Capsaicin pretreatment nearly eliminated the labeled sensory fibers as expected. These data indicate that the trigeminal innervation to the cochlea could be involved in inner ear homeostatic disturbances, including the hydrops that is symptomatic of Ménière's disease.

Animals↗
PubMed1998

The vascular mechanism of action of betahistine in the inner ear of the guinea pig.

The aim of this study was to investigate the mechanism and site of action of betahistine dihydrochloride in the inner ear of the guinea pig. Betahistine-evoked increases in cochlear blood flow (CBF) have been presumed to be due to the drug effect on the later wall capillary bed or larger feeding vessels in the cochlea vascular system. As such, the mechanism of action could be due to inhibition of H3 receptors. Betahistine may also have a direct effect on postsynaptic H1/H2 receptors and/or an effect modulated by other autonomic receptors. Betahistine-evoked CBF responses were assessed by laser Doppler flowmetry in the presence of an H3 agonist (alpha N-methyl-histamine dihydrochloride), an H3 antagonist (thioperamide), an H2 antagonist (cimetidine) or an alpha 2 antagonist (idazoxan). The effects of betahistine on circulation in the anterior inferior cerebellar artery (AICA) and ipsilateral stria vascularis (SV) were assessed using intravital microscopy (IVM). Findings showed that betahistine increased CBF and reduced systemic blood pressure (BP). In contrast, alpha N-methylhistamine dihydrochloride had no effect on baseline CBF or BP and did not influence betahistine-induced increases in CBF. Thioperamide reversed the effects of betahistine on CBF, but had no effect on baseline CBF or BP. Cimetidine had no marked effect on baseline CBF or betahistine-induced increases in CBF Idazoxan had no consistent effects on baseline CBF, but abolished the effect of betahistine on CBF. The mean increase of red blood cell velocity in SV capillaries was 15% and occurred without a demonstrable change in capillary diameters. In contrast, the diameter of the AICA increased by 17-20%, indicating that betahistine-evoked increases in CBF resulted primarily from vasodilatation of the AICA. We suggest that this effect may be mediated via presynaptic H3 heteroreceptors and autonomic alpha 2 receptors.

Animals↗
PubMed1998

Direct evidence of trigeminal innervation of the cochlear blood vessels.

This paper provides the first detailed description of the trigeminal innervation of the inner ear vasculature. This system provides a newly discovered neural substrate for rapid vasodilatatory responses of the inner ear to high levels of activity and sensory input. Moreover, this discovery may provide an alternative mechanism for a set of clinical disturbances (imbalance, hearing loss, tinnitus and headache) for which a central neural basis has been speculated. Iontophoretic injections of biocytin were made via a glass microelectrode into the trigeminal ganglion in guinea-pigs. Tissue for histological sections was obtained 24 h later. Labeled fibers from the injection site were observed as bundles around the ipsilateral spiral modiolar blood vessels, as individual labeled fibers in the interscala septae, and in the ipsilateral stria vascularis. The dark cell region of the cristae ampullaris in the vestibular labyrinth was also intensively labeled. No labeled fibers were observed in the neuroepithelium of the cristae ampullaris or the semicircular canals. These results confirm and localize an earlier indirect observation of the trigeminal ganglion projection to the cochlea. This innervation may play a role in normal vascular tone and in some inner ear disturbances, e.g., sudden hearing loss may reflect an abnormal activity of trigeminal ganglion projections to the cochlear blood vessels.

Animals↗
PubMed1998

Changes in cochlear blood flow due to intra-arterial infusions of angiotensin II (3-8) (angiotensin IV) in guinea pigs.

The effects of a newly discovered form of angiotensin, angiotensin IV (ANGIV), on cochlear blood flow (CBF) have been investigated utilizing the laser Doppler flowmetry (LDF) technique. Two specific questions were addressed: What are the effects of anterior inferior cerebellar artery infusions (AICA) of ANGIV on CBF and do angiotensin fragments other than ANGIV influence CBF in mature male and female guinea pigs. Infusions of ANGIV, and C-terminal shortened fragments were accomplished via micropipette into the AICA and changes in CBF were observed using LDF. The results demonstrated that 10 and 100 pmol/min doses of ANGIV increased CBF 22% and 75% (n = 6; P < 0.01) from baseline, respectively, with little change in mean arterial blood pressure (MAP). Pretreatment with the ANGIV antagonist divalanal-ANGIV (1 nmole/min) blocked increases in CBF due to infusions of 100 pmol/min of ANGIV. The infusion of the C-terminal shortened fragment ANGIV(1-5) and saline had no significant effect on either CBF or MAP. These results provide the evidence for a new subtype of the angiotensin receptor and indicate the likely role of circulating hormones in blood flow regulation in the inner ear.

Amino Acid Sequence↗
PubMed1998

Acoustical modulation of electrically evoked otoacoustic emission in intact gerbil cochlea.

In order to study the interaction between mechanical-electrical and electrical-mechanical transductions of outer hair cells (OHCs) in vivo, we observed the acoustically induced changes in the electrically evoked otoacoustic emission (EEOAE). One pole of a bipolar electrode was placed in the round window niche and the other pole on the surface of the first cochlear turn in the gerbil. A microphone and a speaker were used to monitor the EEOAE and to deliver an acoustical tone, respectively. It was found that a high sound level acoustical tone enhanced the EEOAE fine structure at frequencies below the acoustical frequency, and suppressed the overall level of the EEOAE at frequencies above the acoustical frequency. In addition, the EEOAE at frequencies approximately one half octave lower than the acoustical frequencies were relatively more enhanced or showed relatively less suppression than at other frequencies. The amplitudes of these changes had a positive relationship with acoustical tone levels. Furosemide eliminated the acoustically caused EEOAE change indicating that the acoustically caused change in the EEOAE is a phenomenon of the normal cochlea. One possible mechanism for the results is that the electrically and acoustically evoked basilar membrane (BM) vibrations interact at the EEOAE generation site and change the local mechanical and electrical properties. The second possible mechanism is that the acoustical stimulus creates an impedance discontinuity at its characteristic frequency location leading to a change in the reflected electrically evoked traveling wave, which may enhance or suppress the EEOAE by the vector summation of two waves.

Acoustic Stimulation↗
PubMed1998

Age-related changes in cochlear blood flow response to occlusion of anterior inferior cerebellar artery in mice.

Previous studies suggest that autoregulation of cochlear blood flow (CBF) may be impaired by aging. In this study, we quantified the capacity of CBF autoregulation in young adult (6-month-old) and aged (21-month-old) CBA mice, to examine the effect of aging on CBF autoregulation. The technique of anterior inferior cerebellar artery (AICA) occlusion was employed to manipulate cochlear perfusion pressure. The CBF was measured by laser Doppler flowmetry during intermittent occlusion of the AICA with a microvascular clamp, which causes an initial decrease in CBF. The autoregulation of CBF was evaluated by quantifying the CBF increase (compensatory dilatory response in the cochlear vessels) during AICA occlusion. Our results demonstrated that autoregulation of CBF was significantly reduced and that collateral vascular function supplying CBF was significantly lower in the aged group. These findings suggest that the aged ear has less capacity to maintain stable blood flow and thus may be more vulnerable to stress factors that affect cochlear function.

Age Factors↗
PubMed1997

Trigeminal ganglion innervation of the cochlea--a retrograde transport study.

Innervation patterns of sensory nerves from the trigeminal ganglion to the cochlear blood vessels were studied using retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase. Guinea-pigs (n=7) were unilaterally implanted with an osmotic pump and a cannula for cochlear delivery of 2% or 20% wheat germ agglutinin horseradish peroxidase (Group 1), 2% wheat germ agglutinin-horseradish peroxidase followed by 100 micromol capsaicin (Group 2), or vehicle alone. Histological sections of the trigeminal ganglia, the C1 and C2 dorsal ganglia, the superior and inferior ganglia of the glossopharyngeal nerve bilaterally, the midbrain and the brainstem were obtained after 48 h of infusion. In Group 1, a large number of labeled nerve cell bodies were observed in the anteromedial portion of the trigeminal ganglion and at the origin of the ophthalmic nerve. Some labeled cells were also found on the lateral side of the ophthalmic nerve, as well as on the medial side of the maxillary nerve root. Capsaicin pretreatment significantly reduced the density of labeled neurons in the trigeminal ganglion. A few labeled neurons were also found in the trigeminal brainstem nucleus complex and in certain auditory brainstem nuclei. No wheat germ agglutinin horseradish peroxidase-positive cells were observed in the spinal C1 or C2 cervical ganglia or in the superior or inferior glossopharyngeal ganglia. In contrast, wheat germ agglutinin-horseradish peroxidase application to the middle ear resulted in labeled cells in the middle posterolateral portion of the trigeminal ganglia and in the superior ganglia of the glossopharyngeal nerve. These results provide the first direct evidence that the trigeminal ganglion sends projections to the cochlea.

Animals↗
PubMed1997

The tonic sympathetic input to the cochlear vasculature in guinea pig.

Vascular tones is an essential component in maintaining steady regional blood flow and dynamic responsiveness of a vascular bed. Sympathetic innervation can contribute to vascular tone. Although certain studies have reported evoked changes in cochlear blood flow (CBF) with activation of the sympathetic fibers to the cochlear vasculature, other studies have failed to show evidence of sympathetic contribution to CBF regulation when the cervical sympathetic fibers were unilaterally sectioned. We hypothesized that the bilateral 'sympathectomy of the stellate ganglia' would remove sufficient sympathetic input to the cochlea to yield a change in CBF resting level. To test this hypothesis a new technique was used to expose the stellate ganglia (SG) bilaterally and induce a chemical sympathectomy. We observed that unilateral SG blockade with 2 microliters of 4 mM lidocaine hydrochloride on either side produced a 5-10% increase in CBF, which recovered to baseline during the following 2 min. A subsequent blockade of the contralateral SG produced a rapid 25-35% increase, which then recovered partially during the following 3-4 min, remaining 5-15% above the baseline over a 20 min measurement period. Superior cervical ganglion transection did not affect CBF. Our results provide evidence for the existence of a tonic sympathetic component in the control of vascular tone in guinea pig cochlea. This neural effect is derived bilaterally from SG. This result is consistent with previous anatomical studies showing the bilateral innervation of the cochlea by the SG sympathetic fibers and with previous physiological studies on the bilaterality of evoked changes in CBF due to electric stimulation of SG.

Anesthetics, Local↗
PubMed1997

ATP-induced cochlear blood flow changes involve the nitric oxide pathway.

Although control mechanisms of cochlear blood flow (CBF) have been intensively studied since laser Doppler flowmetry was introduced for CBF measurement in animals and humans, the role of adenosine 5'-triphosphate (ATP) in CBF regulation is not known. Since ATP is a potent vasoactive agent in other organs, the aim of this study is to examine ATP-induced changes in CBF and to test whether the nitric oxide pathway is involved in ATP-induced CBF changes. The anterior inferior cerebellar artery (AICA) of anesthetized pigmented guinea pigs was exposed, and ATP was perfused into the AICA. For CBF measurement, the bulla was opened and the 0.7 mm laser probe of a Perimed PF2B flowmeter was positioned on the basal turn of the cochlea. AICA perfusion of an ATP solution caused dose-dependent transient CBF increases. The maximum CBF increase induced was 220% of the baseline. In some animals, CBF showed a dual effect; a transient decrease followed by a longer-lasting increase. The perfusions of sodium nitroprusside (SNP) also resulted in dose-dependent CBF changes. The intravenous application of N(omega)-nitro-L-arginine methyl ester (L-NAME) significantly attenuated ATP-induced CBF increases, and enhanced ATP-induced decreases, but did not affect SNP-induced CBF changes. The ATP-induced CBF responses indicate that ATP plays a role in CBF regulation. The biphasic characteristic of the ATP-induced CBF change suggests the involvement of both P2x- and P2y-subtype purinoceptors. That L-NAME caused attenuation of the ATP-induced CBF increase implies that the ATP-induced CBF increase is mediated by the release of endothelium-derived relaxing factor, nitric oxide, following activation of endothelial P2y-purinoceptors in the cochlear vascular bed and/or cochlear supplying vessels.

Adenosine Triphosphate↗
PubMed1997

Basilar membrane velocity noise.

Basilar membrane (BM) noise, measured as a velocity signal under the quiet acoustic condition, was investigated in the guinea pig. The cochleas of anesthetized young healthy guinea pigs were surgically exposed and a hole was made on the lateral wall of the scala tympani of the first cochlear turn for visualization of the BM and measurement of the BM velocity with a laser interferometer. The amplitude and frequency of the BM velocity noise were analyzed by a spectrum analyzer under different conditions. The spectrum of the BM velocity noise was a band limited function with a peak velocity at the topographic best frequency of the measured location on the BM. The peak velocity ranged to about 8 microm/s and depended on the physiological condition of the cochlea. Saline blockage of the external auditory canal or the middle ear did not change the BM noise. BM noise was much smaller, or was not evident, when the cochlear sensitivity decreased. The suppression tuning curve of the BM velocity noise indicates that the maximum suppression caused by an acoustic pure tone occurred at the best frequency location. A low sound level wide band acoustic noise given to the external ear canal produced a spectrum function having the same frequency and amplitude response as the BM noise. Electrical stimulation of the crossed olivocochlear bundle significantly depresses the BM velocity noise. These data demonstrate that the BM noise is a representation of internal rather than external noise. The amplitude and frequency of the BM noise reflect the usual cochlear sensitivity and frequency selectivity. Since the organ of Corti in the sensitive cochlea is a highly sensitive and tuned mechanical system, the internal (to the animal) noise responsible for the BM noise may originate from mechanical vibrations remote from the cochlea and propagated to the ear, or may be caused by Brownian motion of cellular structures in the cochlea.

Acoustic Stimulation↗
PubMed1997

The mechanical waveform of the basilar membrane. I. Frequency modulations ("glides") in impulse responses and cross-correlation functions.

The purpose of this investigation is to present evidence from experimental as well as model results on temporal variations of the frequency of oscillation in the basilar membrane's impulse response. Stimuli were either clicks leading to a direct estimate of the impulse response, or bands of pseudo-random noise (one or two octaves wide) which lead to an indirect estimate of the impulse response via a cross-correlation procedure. The noise bands were centered at the best frequency of the BM location under observation. Responses were obtained from the basal turn of the guinea-pig cochlea, from a location with a best frequency (for the weakest stimuli) between 17.0 and 18.5 kHz. Data acquisition was done with a sample frequency of 208 kHz. Input-output cross-correlation functions were found to share with impulse responses the property that the initial oscillations have a noticeably lower frequency than the later ones. During the impulse response the frequency of oscillation increases gradually. This increase occurs and continues to beyond the time that the oscillations reach the largest amplitude. This frequency variation is called a "glide." Using the "analytic signal" method the frequency of oscillation is found to increase continually throughout the duration of the main lobe of oscillation, even at the lowest tested stimulus intensities (about 20 dB SPL). At high stimulus intensity both the direct and indirect impulse response change their appearance drastically but the glide retains its basic form. In the case of the direct impulse response estimate the glide can be attributed to temporal variation of the degree of nonlinearity. For the indirect impulse response this is not true, because with a constant level noise stimulus there is no regular temporal variation of nonlinearity. In this case the glide should be interpreted as an intrinsic property of the cochlear system. From our and others' data the glide was found to exist over a topographic frequency range of best frequencies of at least from 1.76 to 18 kHz. Two examples of present-day models of the cochlea are discussed of which one is found to demonstrate the glide phenomenon in its response, and the other one does not.

Acoustic Stimulation↗
PubMed1997

Two-tone suppression of basilar membrane vibrations in the base of the guinea pig cochlea using "low-side" suppressors.

The responses of the basilar membrane (BM) in the basal section of the guinea pig cochlea were measured by laser interferometry. The stimuli were pairs of harmonically related tones, presented simultaneously. One tone, at the BM's characteristic frequency (CF) of about 17 kHz, was presented at a low intensity. The other tone, presented at various intensities, was a "low-side" suppressor, with a frequency of 0.2-8 kHz. As observed by many others, the suppressor tone, when presented at high enough intensity, reduced the magnitude of the CF component of BM displacement, sometimes dramatically. However, regardless of whether the CF component was suppressed or not, the sum of the displacement amplitudes of the CF and suppressor components was always greater than the displacement amplitude of the unsuppressed CF component. For suppressor frequencies up to 4 kHz, the suppression was both tonic and phasic, and synchronized to the suppressor period. For higher suppressor frequencies, principally tonic suppression was seen.

Acoustic Stimulation↗
PubMed1997

Frequency-dependent enhancement of basilar membrane velocity during olivocochlear bundle stimulation.

Basilar membrane (BM) velocity responses were measured in the presence of olivocochlear bundle (OCB) stimulation. Frequency threshold tuning curves (FTCs) were derived from tone-evoked input-output (I/O) functions. Efferent nerve activation produced decreases in velocity amplitude for frequencies around best frequency (BF) at low stimulus levels with little or no effect for stimuli well below the BF. A level-dependent efferent reduction/enhancement of BM velocity was found for certain stimulus frequencies above the BF. Efferent activation either had no effect or caused small reductions in the velocity response produced by low level sound, whereas, at higher stimulus levels, efferent activation increased the velocity response. The derived FTCs, therefore, showed criterion-dependent changes with efferent activation. For low BM criterion velocities, FTCs showed the classic desensitization of the tip region without a shift of BF. Some BM velocity criterion values showed FTCs with an expanded high-frequency response area, also without a shift of BF. The results suggest that the effect of OCB activation changes the gain of the voltage-dependent outer hair cell motility such that BM velocity response near BF is decreased while increasing the response for tones well above BF.

Acoustic Stimulation↗