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Biomedical subjects

A F Ryan

Publications and source records attributed to A F Ryan.

At least 91 records · Page 5Linked to original sources
PubMed1991

Homing of lymphocytes to the inner ear.

The migration of lymphocytes to the inner ear was studied during an immune response in the cochlea. Sensitized lymphocytes from peripheral blood, neck lymph nodes and spleen from strain 13 inbred guinea pigs were labelled with 51Cr and injected intravenously into strain 13 recipients undergoing an inner ear immune response. Eighteen hours later the temporal bones and immune organs of the recipients were assayed for radioactivity to detect the infiltration of labelled cells. In addition autoradiography was performed to localize labelled cells in the inner ear. More lymphocytes from the peripheral blood entered the inner ear during the immune response than spleen or lymph node cells. This indicates that the inner ear comes under the immuno-surveillance of the peripheral circulation in response to antigenic stimulation. Most labelled lymphocytes were observed in the basal turn of the scala tympani and in and around the spiral modiolar vein of the challenged cochlea. A few cells were seen also in the control cochleas but almost all where inside the blood vessels. This pattern suggests that the blood vessels of the spiral modiolar vein are the initial site through which lymphocytes entered the inner ear.

Animals↗
PubMed1990

Collaterals from lateral and medial olivocochlear efferent neurons innervate different regions of the cochlear nucleus and adjacent brainstem.

Two populations of superior olivary neurons which project to different sensory cell regions in the cochlea also give off collateral projections to the ventral cochlear nucleus (VCN) and adjacent brainstem. To determine whether these VCN projections also have different targets they were characterized by selective retrograde amino acid transport. Retrograde transport of 3H-d-aspartate (D-ASP) selectively labeled the unmyelinated fibers and neurons of the lateral olivocochlear (OC) system including a dense collateral projection to the central VCN. Retrograde transport of 3H-nipecotic acid (NIP) labeled the myelinated fibers and neurons of the medial OC system, including collateral projections to the peripheral VCN, subpeduncular granule cells, and nucleus Y. Medial and lateral OC efferent collaterals thus innervate different regions of the CN. Lateral system collaterals overlap extensively with Type I spiral ganglion cell afferent input. They are well positioned to play a role in modulating afferent input to the central auditory system, as is the primary projection of these efferents to the cochlea. The medial system collaterals project near the recently described afferent projections of Type II spiral ganglion cells. The medial system collaterals may therefore be related to the function of outer hair cells, as the medial system primary axons appear to be in the cochlea.

Animals↗
PubMed1990

Autoradiographic studies of selective amino acid uptake by neural and nonneural elements in the gerbil cochlea.

The cochlea is well suited for studies of the uptake properties of auditory neurons and nonneuronal supporting cells. Probe concentrations of radioisotopically labeled amino acids, including putative neurotransmitters and their precursors, breakdown products, and blockers, can be introduced via the natural, fluid-filled channels of the inner ear. Uptake patterns can be mapped at cellular and intracellular levels using light and electron microscopic autoradiographic methods. The procedures for introduction of label, fixation, plastic embedment, and light and electron microscopic autoradiography are described with special reference to the cochlea. Labeling patterns observed with over 20 amino acids are summarized for hair cells, spiral ganglion neurons, efferents, and nonneural elements of the stria vascularis, limbus, and modiolus. Limitations on the interpretation of results and their implications for the general usefulness of the methods are discussed.

Amino Acids↗
PubMed1990

Comparison of immune-mediated models of acute and chronic otitis media.

The distribution of immunoglobulin-bearing cells and the pattern of histopathological changes in the middle ear (ME) mucosa, round window membrane (RWM), and inner ear were compared during acute and chronic immune-mediated otitis media with effusion (OME) in the guinea pig as an animal model. In both acute and chronic immune responses (IRs), mucosal hyperplasia, edema, neovascularization, and cellular infiltration were observed. IgG+ cells were predominant in both the acute and chronic IRs. The number of IgA+ cells, however, increased in the mucosa and RWM during chronic IRs. Only the chronic IR resulted in gland formation within the ME and inflammation within the cochlea. These results indicate that the chronic IR was more similar to reports of clinical OME than the acute IR. The cochlear inflammation associated with chronic OME can lead to sensorineural hearing loss, as reported in clinical studies.

Acute Disease↗
PubMed1990

Spatial distribution of neural activity evoked by electrical stimulation of the cochlea.

Activity in the central auditory system was mapped with 2-deoxyglucose (2-DG) autoradiography, using either pure tones or electrical stimulation of the normal cochlea. Electrical stimulation with both monopolar (distant reference electrode) and bipolar prostheses near threshold increased 2-DG uptake in auditory nuclei in a manner similar to that seen with a pure tone: increased 2-DG uptake was restricted to a small frequency region of brainstem and mid-brain auditory nuclei. The position of this area was related to the cochlear location of the prosthesis. At higher current amplitudes only the bipolar prosthesis retained spatial restriction of evoked neural activity, while stimulation through a monopolar prosthesis produced evoked activity in all frequency regions of auditory nuclei, and in non-auditory nuclei. Activation of non-auditory structures was consistent with spread of current through the brainstem, rather than activation of peripheral nerves. At all current amplitudes, a monopolar prosthesis evoked higher levels of 2-DG uptake than a bipolar prosthesis. The results suggest that while a bipolar prosthesis provides greater spatial restriction of evoked neural activity and a greater dynamic range, a monopolar prosthesis produces higher levels of evoked activity.

Acoustic Stimulation↗
PubMed1989

Auditory neural activity evoked by pure-tone stimulation as a function of intensity.

The 2-deoxyglucose (2-DG) autoradiographic technique was employed to map activation of the central auditory pathway in the mongolian gerbil during stimulation with a 3.0 kHz tone at several intensities. In most auditory nuclei, the tone produced restricted areas in which 2-DG uptake was markedly higher than that of adjacent tissue, at locations consistent with the known tonotopic organization of the structure. The size of these regions changed relatively little with increasing stimulus intensity from 25 to 65 dB SPL (re 0.0002 dyne/cm2). At higher intensities, evoked uptake spreads into locations which represent frequencies above 3.0 kHz. In the inferior colliculus, relative 2-DG uptake decreased with increasing stimulus intensity in bands on either side of the 3.0 kHz region. These bands of reduced uptake became wider with increasing stimulus intensity from 25 to 85 dB SPL. The optical densities of auditory structures were normalized by the density of non-auditory white matter to derive optical density ratios. In the cochlear nuclei, optical density ratios in the 3.0 kHz region increased monotonically with increasing stimulus intensity, to a plateau at 45 dB SPL. In higher auditory nuclei, relative 2-DG uptake increased to a peak at 45 dB SPL and then declined at higher intensities.

Action Potentials↗
PubMed1989

Spiral ganglion cell density in young and old gerbils.

The Mongolian gerbil, like other mammalian species, has a decreased number of spiral ganglion cells as a function of age. This loss of cells was first seen in 24- to 30-month old animals in the basal end of the ganglion. In the oldest individuals the apical end of the ganglion was also affected. There were approximately 15-25% fewer cells in the affected areas in the 36- to 42-month old animals. In the oldest animals degeneration of the stria vascularis was seen in the apical turn and some degenerative changes in the organ of Corti were seen throughout the length of the cochlear duct. The aging pattern in the gerbil cochlea, is similar to that described for other species. Vacuoles, previously described in the gerbil cochlear nucleus, were also seen in the auditory nerve within the modiolus, but central to the Schwann-glial border in all animals. Vacuoles were not present within the spiral ganglion or the peripheral processes of the ganglion cells. Because the ganglion cell axons should be similar on either side of the Schwann-glial border, but the vacuoles were confined to the central nervous system, it is concluded that the degenerative process affects glial cells as opposed to neurons.

Aging↗
PubMed1989

Modulation of middle ear immune response by gut immunization.

Swallowing of upper respiratory pathogens which may at another time be involved in otitis media with effusion (OME) undoubtedly occurs in many patients. In order to explore the possible immunologic consequences to the middle ear (ME) of such gut exposure, guinea pigs were fed antigen either before or after systemic sensitization. A ME immune response was then elicited by ME antigenic challenge. Feeding before systemic sensitization induced systemic tolerance and blunted both the ME immune response and immune-mediated OME. Feeding after systemic sensitization amplified ME immunity and increased immune-mediated OME. Gut immunization, therefore, provides a potent modulation of ME immune response. Depending upon its timing, pathogen swallowing could produce immune hyporesponsiveness, with lowered resistance to infection but reduced immune-mediated inflammation. Alternatively, swallowing could result in immune hyperresponsiveness, with increased resistance but also increased inflammation.

Animals↗
PubMed1988

Contributions of the middle ear to the development of function in the cochlea.

The contribution of middle ear immaturities to the development of cochlear microphonic potential (CM) responses was studied throughout the ontogeny of auditory function in the Mongolian gerbil. CM produced by direct mechanical stimulation of the stapes was compared with CM generated by acoustic stimulation of the intact ear at various postnatal ages. The results indicated that during development acoustically generated CM reflects middle ear as well as inner ear maturational factors. With direct stapes driving, CM was first elicited at 10 days after birth (DAB), two days earlier than with acoustic stimulation. Controlling for the contributions of middle ear immaturity, maturation of the inner ear accounted for approximately a 75 dB improvement in CM thresholds between 10 and 18 DAB. Comparisons between the results obtained with the acoustic and stapes driving stimulation protocols suggested that the major maturational changes in the middle ear conduction apparatus occurred between 14 and 16 DAB. This period was associated with the final stages of resorption of middle ear mesenchyme and ossicular ossification. Before 16 DAB, acoustically evoked CM thresholds reflect approximately a 25 dB loss in sensitivity due to middle ear immaturity.

Acoustic Stimulation↗
PubMed1988

Development of tonotopic representation in the Mongolian gerbil: a 2-deoxyglucose study.

The spatial representation of frequency in the central auditory system of the neonatal gerbil was mapped with the 2-deoxyglucose (2-DG) autoradiographic technique. At 14 days after birth (DAB), pure tone stimulation produced recognizable patterns of 2-DG uptake. However, at this age, tone-induced areas of increased 2-DG uptake occurred at locations which in the adult respond to higher frequencies. The degree of shift in tonotopic representation was approximately two octaves. The normal adult tonotopic organization of auditory nuclei was achieved by 18 DAB, consistent with the rapid development of auditory function in the gerbil. The results suggest that the spatial distribution of frequency in the cochlea of neonatal animals is different from that in adults. Stimulus-evoked 2-DG uptake occurred first in brainstem auditory nuclei, and was observed in midbrain and forebrain auditory structures only at later ages. This is consistent with a sequential development of function in the central auditory pathway.

Acoustic Stimulation↗
PubMed1988

The spatial representation of frequency in the rat dorsal cochlear nucleus and inferior colliculus.

The spatial distribution of neural activity produced by tones was assessed in the rat dorsal cochlear nucleus (DCN) and inferior colliculus (IC), using the 2-deoxyglucose (2-DG) technique. Eight pure tones, spanning the range of reported single unit characteristic frequencies in the rat, were presented at 40 dB above behavioral threshold. The relationship between frequency of stimulation and location of neural activity within each nucleus was evaluated quantitatively. Based on the 2-DG uptake pattern across animals, a tonotopic axis in the transverse plane was defined for each nucleus. This axis transected the centers of regions of evoked 2-DG uptake for each frequency. There was an orderly relationship between stimulus frequency and the location of evoked neural activity along the axis. Each pure tone stimulus activated an approximately equal proportion of this axis, for all frequencies tested, in both the DCN and IC. This suggests the existence of equal 'spatial bandwidths, in rat central auditory structures, across its entire frequency range. Equal spatial bandwidths could facilitate signal analysis strategies which require interaction between neurons with closely-related CFs. In the horizontal plane, however, the proportion of stimulated tissue was not equal across frequency. High-frequency (greater than 8 kHz) tones produced increased neural activity along a much greater extent of the anterior-to-posterior axis of the IC than did low-frequency tones.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Ultrastructural characterization of gerbil olivocochlear neurons based on differential uptake of 3H-D-aspartic acid and a wheatgerm agglutinin-horseradish peroxidase conjugate from the cochlea.

Two populations of olivocochlear (OC) neurons have been identified in the gerbil brain stem on the basis of differential labeling patterns of 3H-D-aspartic acid (D-ASP) and wheatgerm agglutinin-horseradish peroxidase conjugate (WGA/HRP) from the cochlear perilymph. While both populations are capable of uptake and retrograde uptake of WGA/HRP, one population accumulates and retrogradely transports D-ASP (D-ASP OC neurons) and the other does not (non-D-ASP OC neurons). D-ASP OC neurons are found in or near the lateral superior olive, are small in size, and receive very few synaptic contacts. The vast majority of these synapses contain small, mildly pleomorphic vesicles with scattered dense core vesicles. Synapses with distinctly larger pleomorphic vesicles have also been observed. These neurons possess all of the features common to neurons of the lateral olivocochlear system. Non-D-ASP OC neurons are found primarily in the ventral nucleus of the trapezoid body, as well as in the area between the medial superior olive and the medial nucleus of the trapezoid body. These neurons are larger and receive greater numbers and types of synaptic contacts than those found on D-ASP OC neurons. The 2 most common synapses found on non-D-ASP OC neurons are axosomatic ones containing small, mildly pleomorphic vesicles and scattered dense core vesicles similar to those seen on the D-ASP OC neurons, and axodendritic synapses containing large, round vesicles. Much less frequently observed are synapses containing small, round vesicles or ones containing predominantly flat vesicles. The ultrastructural features of the non-D-ASP OC neurons correspond to those described for neurons of the medial olivocochlear system.

Animals↗
PubMed1987

Selective retrograde labeling of lateral olivocochlear neurons in the brainstem based on preferential uptake of 3H-D-aspartic acid in the cochlea.

We have previously shown that perfusion of the gerbil cochlea with probe concentrations of 3H-D-aspartic acid (D-ASP) results in immediate, selective labeling of 50-60% of the efferent terminals under the inner hair cells, presumably by high-affinity uptake. The present study was undertaken to determine the origin of these endings. Twenty-four hours after cochlear perfusion with D-ASP, labeled neurons were observed in the ipsilateral, and to a much lesser extent in the contralateral, lateral superior olivary nucleus (LSO). The cells were small, primarily fusiform, and showed fewer synaptic contacts than other LSO cells. Combined transport of D-ASP and horseradish peroxidase indicated that all olivocochlear neurons within the LSO that projected to the injected cochlea were labeled by D-ASP. Labeled fibers coursed dorsally from the LSO, joined contralateral fibers that had passed under the floor of the fourth ventricle, and entered the VIIIth nerve root at its ventromedial edge. Adjacent to the ventral cochlear nucleus (VCN), densely labeled collateral fibers crossed the nerve root to enter the VCN. Labeled fibers and terminals were prominent in the central VCN. Neither retrograde transport of D-ASP by medial olivocochlear and vestibular efferents nor anterograde transport by VIIIth nerve afferents was observed. The D-ASP-labeled cells and fibers are clearly lateral olivocochlear efferents. Retrograde transport of D-ASP thus allows the cells, axons, and collaterals of the lateral olivocochlear system to be studied, morphologically, in isolation from other cells that project to the cochlea. Since the olivocochlear neurons are almost certainly cholinergic, retrograde amino acid transport does not necessarily identify the primary neurotransmitter of a neuron. Rather, it indicates the presence of selective uptake by the processes of that neuron at the site of amino acid injection. Retrograde labeling appears to be markedly enhanced by the use of metabolically inert compounds such as d-isomer amino acids.

Animals↗
PubMed1987

Pentobarbital and ketamine alter the pattern of 2-deoxyglucose uptake in the central auditory system of the gerbil.

Relative 2-deoxyglucose (2-DG) uptake was investigated during pentobarbital and/or ketamine anesthesia, when animals were either kept in silence or stimulated with wide band noise at 85 dB SPL. In the absence of anesthesia, noise stimulation produced a large increase in relative 2-DG uptake, when compared to silence, in all auditory nuclei up to and including the inferior colliculus. Much more modest noise-induced increases were seen in the medial geniculate nucleus and auditory cortex. These effects were markedly altered by anesthesia. Pentobarbital, and especially pentobarbital plus ketamine, enhanced stimulus-evoked increases in relative 2-DG uptake in lower auditory nuclei: the cochlear nuclei, superior olivary complex and ventral nucleus of the lateral lemniscus. At the same time, stimulus-evoked increases were decreased in the dorsal nucleus of the lateral lemniscus and inferior colliculus, and virtually eliminated in the medial geniculate and auditory cortex. The results of this study permit more meaningful comparison of 2-DG techniques with electrophysiological measures of central auditory activity, and illuminate the utility and limitations of each method. The data indicate that 2-DG observations from barbiturate-anesthetized preparations should be interpreted with some caution. They further suggest that the 2-DG technique is inappropriate for the study of stimulus-evoked activity in the medial geniculate and auditory cortex of barbiturate-anesthetized animals.

Acoustic Stimulation↗
PubMed1986

Nipecotic acid: preferential accumulation in the cochlea by GABA uptake systems and selective retrograde transport to brainstem.

[3H]Nipecotic acid was shown to be preferentially accumulated by the same cochlear structures which selectively accumulate [3H]gamma-aminobutyric acid ([3H]-GABA), including the terminals of a subset of olivocochlear neurons. With both amino acids, olivocochlear fibers selectively transported label in a retrograde direction, from cochlea to brainstem. However, only [3H]nipecotic acid produced dense labeling, and labeling of cell bodies in the superior olive, presumably because it is metabolized very slowly. Nipecotic acid appears to provide a selective retrograde tracer, specific to neurons whose terminals exhibit preferential GABA uptake.

Animals↗
PubMed1986

Regional differences of brain glucose metabolic compensation after unilateral labyrinthectomy in rats: a [14C]2-deoxyglucose study.

A unilateral labyrinthectomy was performed on anesthetized adult albino rats. Brain [14C]2-deoxyglucose (2DG) uptake was measured autoradiographically 3.5 h to 20 days later and compared to sham-operated controls. In the vestibular nuclei (nn.) of labyrinthectomized subjects, large left-right differences of 2DG uptake occurred, which decreased over time. The equalization of vestibular nuclear 2DG uptake paralleled behavioral compensation of body, neck and head postural abnormalities, and known equalization of vestibular nuclear cell firing rates during compensation. There was a small difference of 2DG uptake in medial and lateral vestibular nn. 20 days after lesions when animals had a residual head tilt and tonic eye deviation. In the oculomotor nn., trochlear nn. and interstitial n. of Cajal, large left-right differences of 2DG uptake occurred, which did not change over time. The higher 2DG uptake in these nn. occurred ipsilateral to the labyrinthine lesion and did not correlate with the onset and cessation of nystagmus. The persistent asymmetry did appear to correlate with ipsilateral downward and contralateral upward eye deviation which continued for long periods after the lesion. We hypothesize that the non-compensating metabolic asymmetry in the oculomotor and trochlear nn. could be due to lesioned otolithic input to the vestibular nn. which relays to trochlear and oculomotor nn.

Animals↗