Search PubMed⌕ Search

Biomedical subjects

D R Moore

Publications and source records attributed to D R Moore.

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

Conductive hearing loss produces a reversible binaural hearing impairment.

Conductive hearing loss, produced by otitis media with effusion, is widespread in young children. However, little is known about its short- or long-term effects on hearing or the brain. To study the consequences of a conductive loss for the perception and processing of sounds, we plugged the left ear canal of ferrets for 7-15 months during either infancy or adulthood. Before or during plugging, the ferrets were trained to perform a binaural task requiring the detection of a 500 Hz tone, positioned 90 degrees to the right, that was masked by two sources of broad-band noise. In one condition ("control"), both noise sources were 90 degrees right and, in the second condition ("bilateral"), one noise source was moved to 90 degrees left. Normal ferrets showed binaural unmasking: tone detection thresholds were lower (mean 10.1 dB) for the bilateral condition than for the control condition. Both groups of ear-plugged ferrets had reduced unmasking; the mean residual unmasking was 2.3 dB for the infant and 0.7 dB for the adult ear-plugged animals. After unplugging, unmasking increased in both groups (infant, 7.1 dB; adult, 6.9 dB) but not to normal levels. Repeated testing during the 22 months after unplugging revealed a gradual return to normal levels of unmasking. These results show that a unilateral conductive hearing loss, in either infancy or adulthood, impairs binaural hearing both during and after the hearing loss. They show scant evidence for adaptation to the plug and demonstrate a recovery from the impairment that occurs over a period of several months after restoration of normal peripheral function.

Acoustic Stimulation↗
PubMed1999

Cross-modal reorganization of callosal connectivity without altering thalamocortical projections.

Mammalian cerebral cortex is composed of a multitude of different areas that are each specialized for a unique purpose. It is unclear whether the activity pattern and modality of sensory inputs to cortex play an important role in the development of cortical regionalization. The modality of sensory inputs to cerebral cortex can be altered experimentally. Neonatal diversion of retinal axons to the auditory thalamus (cross-modal rewiring) results in a primary auditory cortex (AI) that resembles the primary visual cortex in its visual response properties and topography. Functional reorganization could occur because the visual inputs use existing circuitry in AI, or because the early visual inputs promote changes in AI's circuitry that make it capable of constructing visual receptive field properties. The present study begins to distinguish between these possibilities by exploring whether the callosal connectivity of AI is altered by early visual experience. Here we show that early visual inputs to auditory thalamus can reorganize callosal connections in auditory cortex, causing both a reduction in their extent and a reorganization of the pattern. This result is distinctly different from that in deafened animals, which have widespread callosal connections, as in early postnatal development. Thus, profound changes in cortical circuitry can result simply from a change in the modality of afferent input. Similar changes may underlie cortical compensatory processes in deaf and blind humans.

Afferent Pathways↗
PubMed1999

Continuous monitoring of in vivo nitric oxide formation using EPR analysis in biliary flow.

A method to continuously monitor the nitric oxide (NO) level in anesthetized rats, using an in vivo trapping reaction of NO by iron-dithiocarbamate complex, is reported. Previously, we developed a method of monitoring NO in bile samples containing an NO complex excreted from the liver (Anal. Biochem. 243, 8-14, 1996). In the present study, we modified the method so that the bile flows directly through the EPR sample cell. Rats were injected with low doses of lipopolysaccharide (LPS) to induce NO formation and were later anesthetized. After cannulation, the bile duct was connected to the inlet of the EPR sample cell and the trapping agent iron complex of D-N-methylglucamine dithiocarbamate (MGD-Fe) was administered. The EPR signal level from NO complex of MGD-Fe in the flowing bile was continuously monitored. Using this method, immediate changes in in vivo NO level in rats were observed following administration of drugs that can affect NO formation. In addition, a continuous intravenous saline containing MGD-Fe made the EPR signal level stable and improved animal condition as well as survival time. Therefore, this method has two merits; (1) one can continuously monitor NO formation until it reaches the maximum level; (2) a rapid change in NO level after intervention can be followed. Using this method, we tested the effect of the substrate L-arginine and inhibitors for NO synthase activity and NO synthase induction. The sensitivity of the present method was tested by monitoring NO formation in rats after exposure to ionizing radiation.

Animals↗
PubMed1999

Effects of unilateral cochlear removal on dendrites in the gerbil medial superior olivary nucleus.

For most neurons, dendrites serve as the major pathway for incoming activity from other neurons. It might therefore be expected that dendrites are particularly sensitive to variations in the level of afferent input they receive. In the auditory brainstem, this expectation has been confirmed in neurons of the medial superior olivary nucleus (MSO). The MSO is uniquely suited to studies of afferent influences on dendrites, as lateral and medial dendrites of MSO neurons receive inputs almost exclusively from the ipsilateral and contralateral ears, respectively. Thus, the effects of unilateral afferent manipulations may be compared between defined dendrites on the same neurons. We have used unilateral deafening (by surgical destruction of the cochlea) in immature [postnatal day 18 (P18)] and adult gerbils to study the late maturation and effect of peripheral deafferentation on the dendrites of MSO neurons. In semi-thin, frontal sections from unoperated animals, we found a change between P18 and adulthood from a lateral to a medial bias in the symmetry of MSO dendrites. Cochlear removal in adulthood led to a reduction in the density of dendritic profiles on the side of the ablation in both MSOs. Cochlear removal at P18 led to a rapid (< 3 days) and sustained dendritic atrophy that was most marked in the caudal part of the nucleus. Electron microscope (EM) measurements in the sagittal plane on MSO dendrite profiles of animals unilaterally deafened at P18 showed a reduction in the number, but not in the area, of profiles on the side of the deafened ear. These results demonstrate a developmental change in the symmetry of MSO medial and lateral dendrites, and a rapid and long-lasting reduction in the number of distal dendrites produced by unilateral deafening either in infancy or adulthood.

Animals↗
PubMed1998

Auditory brainstem projections to the ferret superior colliculus: anatomical contribution to the neural coding of sound azimuth.

The mammalian superior colliculus (SC) contains a neural map of auditory space. It is not known whether this topographic representation emerges at the level of the SC or is relayed there from other auditory areas. We have used retrograde labelling techniques in ferrets to examine the sources and pattern of innervation from auditory brainstem nuclei. After multiple injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into the SC, the heaviest concentrations of labelled cells were found in the nucleus of the brachium (BIN) and external nucleus of the inferior colliculus, with much weaker labelling in the nucleus sagulum, dorsal, intermediate and ventral nuclei of the lateral lemniscus, paralemniscal regions, and periolivary nuclei. The projections were predominantly ipsilateral, although labelled cells were found on both sides of the brainstem. Single injections of WGA-HRP or discrete injections of red and green latex microspheres revealed that the caudal and lateral regions of the SC receive the heaviest projections, although the majority of the retrogradely labelled neurons in the contralateral BIN project to rostral SC. On the ipsilateral side, neurons in rostral and caudal regions of the BIN were labelled primarily by the tracer injected into rostral and caudal regions of the SC, respectively. However, no clear segregation was apparent in the BIN after injections into the medial and lateral regions or in any of the other nuclei after either injection paradigm. These data suggest that converging inputs from several auditory brainstem nuclei contribute to the construction of the auditory space map in the SC, although information about sound azimuth may be conveyed to this nucleus via a spatially ordered projection from the ipsilateral BIN.

Animals↗
PubMed1998

Free radical formation during ketamine anesthesia in rats: a cautionary note.

Ketamine is a useful anesthetic agent with good analgesic properties; however, when ketamine was used to anesthetize rats for spin trapping studies of alcohol-induced free radicals, liver extracts contained a strong electron paramagnetic resonance (EPR) signal of a novel radical. The same EPR signal was observed in liver extracts when rats which had not received alcohol were anesthetized with ketamine. When ketamine was added to liver microsomes and NADPH, a nitroxide radical derived from ketamine could be detected in organic extracts. When the spin trapping agent POBN was also added, microsomes produced both a ketamine nitroxide radical and a spin adduct. Similar results were obtained during ketamine oxidation by hydrogen peroxide in a tungstate-catalyzed reaction, or in a Fenton reaction system. The data suggest that the secondary amine group of ketamine can be oxidized to a stable nitroxide which produces an EPR spectrum in the absence of a spin trapping agent. The POBN spin adduct detected may be from a carbon-centered radical in the cyclohexanone ring of ketamine. Because several types of radicals can be formed from ketamine, this agent may not be appropriate as an anesthetic for many types of in vivo spin trapping experiments.

Anesthesia, General↗
PubMed1998

Commissural and lemniscal synaptic input to the gerbil inferior colliculus.

The central nucleus of the inferior colliculus (ICC) receives direct inputs, bilaterally, from all auditory brain stem nuclear groups. To evaluate the contribution made to gerbil ICC neuron physiology by two major afferent pathways, we examined the synaptic responses evoked by direct stimulation of the commissure of the inferior colliculus (CIC) and the ipsilateral lateral lemniscus (LL). Frontal midbrain slices were obtained from postnatal day (P) 9-P19 gerbils, and whole cell recordings were made under current- (n = 22) or voltage-clamp (n = 52) conditions. Excitatory and inhibitory synaptic responses were characterized by sequentially exposing the slice to ionotropic glutamate receptor antagonists [6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) + aminophosphonpentanoic acid (AP-5), or kynurenic acid)], a gamma-aminobutryic acid type A receptor antagonist (bicuculline), and a glycine receptor antagonist (strychnine). In current clamp, LL stimulation typically produced a short latency depolarization followed by a longer duration hyperpolarization. The depolarization was abolished by AP-5 + CNQX, and the remaining inhibitory potential displayed either bicuculline or strychnine sensitivity. In voltage clamp, 79% of ICC neurons displayed synaptic currents after stimulation of each pathway. The synaptic currents were typically complex waveforms, and ionotropic glutamate receptor antagonists reduced inward currents at a holding potential of -80 mV in the majority of neurons. In addition, this treatment reduced outward synaptic currents at a holding potential of -20 mV, indicating that inhibitory interneuronal input was often activated by LL or CIC afferents. A minority of neurons had synaptic currents that were unaffected by glutamate receptor antagonists, but it was more common for CIC-evoked currents to be unaffected (38%) rather than LL-evoked currents (22%). The CIC provided a strong inhibitory input that was almost exclusively GABAergic, whereas the LL inhibition often included a glycinergic component. These experiments have shown that the CIC provides a major glutamatergic and GABAergic input to most ICC neurons. However, much of the inhibitory input from both the CIC and the LL appears to be mediated by interneuronal connections.

Afferent Pathways↗
PubMed1998

Development of cochlear sensitivity to aminoglycoside antibiotics.

This study examined the temporal relationship between aminoglycoside ototoxicity and the onset of auditory function in the rat. A single dose of gentamicin sulfate (200 mg/kg) and furosemide (100 mg/kg) was administered on postnatal day 6 (P6), P7, P8, P9, or P10, just before the onset of auditory function. Ototoxicity was assessed by the elevation of auditory brain stem response (ABR) thresholds, recorded once the rats had matured. The ABRs were evoked by acoustic clicks and tone pips. The thresholds of control and P6- and P7-treated animals did not differ significantly from each other. Thresholds of some P8- and all P9-treated animals were elevated. The P10-treated animals were deafened, according to these ABR criteria. These data suggest that the potential for aminoglycoside ototoxicity develops rapidly between P8 and P10, just before the onset of auditory function.

Animals↗
PubMed1998

Loss of cochlear nucleus neurons following aminoglycoside antibiotics or cochlear removal.

This study compared the effects of aminoglycoside ototoxicity and surgical ablation of the cochlea in infancy on the survival of neurons in the rat cochlear nucleus (CN). Ototoxicity was induced by a single, systemic dose of gentamicin sulfate and furosemide on postnatal day 6 (P6), P7, or P10, and assessed by the elevation of auditory brain stem response thresholds, as described in a companion paper. Unilateral cochlear removals were performed under Saffan anesthesia on P6, P9, and P12. Rats were painlessly sacrificed in adulthood, and the formalin-perfused brains and cochleas were embedded in wax, sectioned, and stained. Ototoxic treatment at P6 through P10 did not reduce neuron counts in the CN. Cochlear removal at P6 resulted in a 40% loss of CN neurons, but removal at P12 did not result in CN neuron loss. These data suggest that the critical period for the dependence of CN neurons on afferent input from the cochlea ends at the same time that susceptibility to aminoglycoside ototoxicity begins.

Animals↗
PubMed1997

Mechanisms for metabolism of ethanol to 1-hydroxyethyl radicals in rat liver microsomes.

Experiments have been designed to reevaluate mechanisms for metabolism of ethanol to 1-hydroxyethyl radicals (HER) in rat liver microsomes. The variables tested include addition of azide, catalase, superoxide dismutase, and deferoxamine, or use of phosphate or Tris buffers. The results indicate that several mechanisms of HER formation are possible, depending on the experimental conditions used to study this process. In the presence of phosphate buffer, which has been used extensively in spite of its ability to chelate iron, HER formation is quite sensitive to changes in hydrogen peroxide availability. These results suggest that Fenton-type reactions produced the oxidizing intermediate responsible for conversion of ethanol to a free radical in phosphate buffer. However, in Tris buffer, HER formation was inhibited markedly by addition of superoxide dismutase, whereas catalase or azide had little effect. These data indicate that the apparent mechanism of radical formation may be influenced by the choice of buffer used. HER formation was almost abolished by the combination of superoxide dismutase and deferoxamine in both buffers, suggesting little enzymatic HER formation by the cytochrome P450 enzymes. When changes in HER formation were compared with rates of ethanol oxidation, it was inferred that 25 to 50% of the acetaldehyde formed during microsomal ethanol oxidation under different experimental conditions could arise via the HER intermediate.

Animals↗
PubMed1997

Naturally occurring neuron death during postnatal development of the gerbil ventral cochlear nucleus begins at the onset of hearing.

Postnatal development of the gerbil ventral cochlear nucleus (VCN) was studied quantitatively under the light microscope in Nissl-stained serial sections at postnatal day 0 (P0), P5, P7, P10, P12, P15, and P140. VCN boundaries were unambiguous at all ages, and nucleus volume was calculated planimetrically for all groups. Measurements of neuron soma cross-sectional area and number were made in all groups except P0. Both VCN volume and soma area doubled between P5 and P10. Although somatic growth did not continue beyond P10, VCN volume increased a further 57% between P15 and P140. Neuron number did not change significantly between P5 and P10, averaging approximately 36,000 neurons. Between P10 and P12, neuron number decreased significantly by 22%, with no further change thereafter. Our data show that, following significant postnatal growth in the gerbil VCN, a brief period of naturally occurring neuron death begins at the onset of hearing.

Aging↗
PubMed1997

Sources of subcortical projections to the superior colliculus in the ferret.

We have identified brainstem and other subcortical afferents to the superior colliculus (SC) in the ferret, by examining the pattern of retrograde labelling that resulted from unilateral injections of red and green fluorescent latex microspheres or of wheat germ agglutinin conjugated to horseradish peroxidase into different regions of this midbrain nucleus. Labelled neurons were found in many structures, including somatosensory, visual and auditory nuclei. These subcortical inputs are almost all bilateral, although most are primarily ipsilateral. Despite some differences in organization, the subcortical projections to the ferret SC broadly resemble those described in other species. Following injections of red and green microspheres in either the rostral and caudal or the medial and lateral regions of the SC, double-labelled cells usually accounted for less than 10% of the total number of retrogradely labelled cells, indicating that most of the subcortical neurons project to discrete regions of the SC. Many of these afferents show some topographic organization, which is much more evident along the rostrocaudal axis of the SC than in the medial-lateral dimension. The intercollicular projection is restricted mainly to the rostral SC and demonstrates a point-to-point organization. Most of the subcortical structures caudal to the central region of the SC were labelled mainly by the tracers injected in caudal SC, while those rostral to this region, including the zona incerta and the pretectal nuclei, were labelled largely by injections in rostral SC. These findings suggest that projections originating from nuclei posterior to the central region of the SC terminate principally in caudal SC whereas afferents from structures anterior to the central region project largely to rostral SC.

Afferent Pathways↗
PubMed1997

Susceptibility of developing cochlear nucleus neurons to deafferentation-induced death abruptly ends just before the onset of hearing.

To investigate the ability of developing cochlear nucleus (CN) neurons to survive in the absence of afferent input, left cochlear removals were performed on gerbils at 2 day intervals from postnatal (P)3 to P11, and at P18 and P93. After a 3 month postsurgical survival period, Nissl-stained frontal sections through the brainstem were analyzed under the light microscope. CN volume, anteroventral cochlear nucleus (AVCN) neuron cross-sectional area, and total number of neurons in the CN were measured on both sides of the brain. Mean volume reduction of the deafferented CN relative to the intact CN ranged between 76% in the P3 group to 33% in the P11 group and did not differ significantly between P11 and P93. Cochlear removal at all ages reduced AVCN neuron cross-sectional area by approximately 40% in the deafferented CN relative to the intact CN, except for the P93 group where neuron atrophy was significantly less severe (23% mean reduction). Massive loss of CN neurons (>50% of the intact side) was observed following cochlear removal performed during the first postnatal week. However, between P7 and P9, neurons in all areas of the CN lose susceptibility to deafferentation-induced neuron death. No significant neuron loss was observed following cochlear removal after P7. This study shows that an abrupt transition in the ability of CN neurons to survive in the absence of afferent input is coincident with events leading to the onset of hearing.

Afferent Pathways↗
PubMed1997

Duration and recurrence of otitis media with effusion in children from birth to 3 years: prospective study using monthly otoscopy and tympanometry.

OBJECTIVE: To monitor the natural course of otitis media with effusion. DESIGN: Prospective, longitudinal assessment of the state of the middle ear by otoscopy and tympanometry at monthly intervals from birth to 3 years. SETTING: Domiciliary visits to family homes. SUBJECTS: 95 full term infants born between August 1991 and November 1993. MAIN OUTCOME MEASURES: Observed and simulated data (Monte Carlo) for the duration of single episodes of otitis media with effusion. RESULTS: 17 of the children had unilateral or bilateral otitis media with effusion for more than half of their first three years of life. Thirty three of the 95 children had tympanograms suggestive of otitis media with effusion at more than a third of observations; the remaining 62 had such tympanograms at less than a third of observations. The data of each group were described by a first order Markov model, yielding a mean duration of unilateral effusion episodes of 5-6 weeks in both groups; the mean duration of bilateral effusion was 6 and 10 weeks in the low and high incidence groups, respectively. However, the main difference between the groups was the time spent between episodes of effusion: effusion free periods were, on average, three times longer in the children who experienced less otitis media with effusion. CONCLUSION: Children who are susceptible to otitis media with effusion tend to have more separate episodes of effusion rather than an increased overall duration of episodes. Such children are primarily distinguished by the likelihood with which they acquire the disease than by their ability to recover from it.

Acoustic Impedance Tests↗
PubMed1997

Changes in lateralization and loudness judgements during one week of unilateral ear plugging.

The aim of this study was to determine whether lateralization judgements show adaptation during a period of unilateral ear plugging. Six normally hearing young adults were tested repeatedly using pure tone stimuli of 500 and 4000 Hz to determine (i) the threshold in each ear, (ii) the interaural sensation level difference (ISLD) at which sounds presented alternately to the two ears were of equal loudness, and (iii) the ISLD at which sounds presented simultaneously to the two ears produced a centered internal sound image. Subjects were tested 9-14 times over one week before an ear plug, producing a nominal attenuation of 21 dB (at both frequencies), was placed in one ear. Subjects wore the plug continuously for a further week, and were tested daily during this period, with the plug in place. After unplugging, subjects were tested less frequently for one final week. Net changes in binaural hearing were measured by subtracting the equal loudness ISLD from the centering ISLD. Four subjects showed no net change, either during or after plugging, but a small (< 3 dB) adaptation occurred during plugging in two subjects.

Adaptation, Physiological↗
PubMed1997

Response properties of neurons in the inferior colliculus of the monaurally deafened ferret to acoustic stimulation of the intact ear.

Response properties of neurons in the central nucleus of the inferior colliculus (ICC) were investigated after unilateral cochlear removal at various ages during infancy. Nineteen ferrets had the right cochlea surgically ablated, either in adulthood or on postnatal day (P) 5, 25, or 40, 3-18 mo before recording. Adult ablations were made on the same day as ("acute," n = 3), or 2-3 mo before ("chronic," n = 3), recording. Two ferrets were left binaurally intact. Single-unit (n = 702) and multiunit (n = 1,819) recordings were made in the ICC of barbiturate-anesthetized ferrets ipsilateral (all ages) or contralateral (P5 and acute adult only) to the intact ear. In binaurally intact animals, tonal stimulation of the contralateral ear evoked excitatory activity at the majority (94%) of recording loci, whereas stimulation of the ipsilateral ear evoked activity at only 33% of recording loci. In acutely ablated animals, the majority of contralateral (90%) and ipsilateral (70%) loci were excited by tonal stimulation of the intact ear. In chronically ablated animals, 80-90% of loci were excited by ipsilateral stimulation. Single-unit thresholds were generally higher for low-best frequency (BF) than for high-BF units, and higher in the ipsilateral than in the contralateral ICC. Analysis of covariance showed highly significant differences between all of the ipsilateral and contralateral groups, but no effects of age at ablation or survival time following ablation, other than that the group ablated at P25 had higher mean ipsilateral thresholds than the groups ablated at P5 or, acutely, in adulthood. Cochlear ablation at P5, 25, or 40 resulted in a significant increase in dynamic ranges of ipsilateral ICC unit rate-intensity functions relative to acutely ablated animals. Dynamic ranges of units in the contralateral ICC of P5-ablated ferrets were also significantly increased compared with those of acutely ablated animals. Cochlear ablation at P5, 25, or 40 resulted in a significant increase in single-unit spontaneous discharge rates in the ICC ipsilateral but not contralateral (P5 only) to the intact ear. These data show that unilateral cochlear removal in adult ferrets leads to a rapid and dramatic increase in the proportion of neurons in the ICC ipsilateral to the intact ear that is excited by acoustic stimulation of that ear. In addition, the data confirm that, in ferrets, cochlear removal in infancy leads to a further increase in responsiveness of individual neurons in the ipsilateral ICC. Finally, the data show that responses in the ICC contralateral to the intact ear are largely but not completely unchanged by unilateral cochlear removal.

Acoustic Stimulation↗
PubMed1997

Free radical formation in livers of rats treated acutely and chronically with alcohol.

The spin trapping method was used to assess formation of free radical intermediates in vivo before and after acute alcohol administration to rats. Ascorbyl radicals and spin adducts of dietary alcohol or endogenous compounds, such as lipids, were detected with higher frequency in bile from alcohol-fed rats than in corresponding samples from rats fed control diets. When alcohol was given acutely to these animals, the 1-hydroxyethyl radical metabolite of ethanol was also formed at higher rates in livers of rats that had been fed ethanol chronically. Furthermore, formation of lipid radicals was enhanced after acute alcohol administration. These data support the hypothesis that chronic alcohol administration causes development of oxidative conditions in the liver, which subsequently lead to formation of differing types of radicals. Liver microsomes from alcohol-fed rats also metabolized ethanol to the 1-hydroxyethyl radical at higher rates than controls.

Alcoholic Intoxication↗