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M D McGinn

Publications and source records attributed to M D McGinn.

At least 19 recordsLinked to original sources

Neuronal degeneration in the gerbil brainstem is associated with spongiform lesions.

Spongiform lesions arise in dendrites and glia in the brainstem of domestic Mongolian gerbils. Most pronounced within the cochlear nucleus (CN), this disorder is dynamic and progressive; the lesions increase in number, size, and extent with age. It has not been clear whether these spongioid lesions either cause or are associated with significant neural degeneration. In contrast, feral Mongolian gerbils (wild-trapped in Tuva) and their offspring show few spongiform lesions. The Tuvan gerbils provide an appropriate within-species control. We compared degeneration in the brainstem of domestic and Tuvan gerbils using the amino-cupric-silver (ACS) stain of de Olmos et al. [(1994) Neurotoxicol. Teratol., 16:545-561]. Positive histologic controls were provided by cerebellar stab wounds in domestic gerbils and by unilateral kainic acid injections into the CN of Tuvan gerbils. The ACS stain revealed extensive degeneration of axons, terminals, dendrites, and neurons in the brainstem of domestic gerbils. Neurodegeneration was most pronounced in the CN and was coextensive with spongiform lesions. Neurodegeneration was also seen in the trapezoid body, lateral lemniscus, and inferior colliculus, but was less pronounced than in the CN. The cerebellar stab wounds resulted in silver-stained Purkinje cells restricted to the stab wound local region. Kainic acid produced extensive neuronal and spongiform degeneration of the injected CN that was very similar to that spontaneously occurring in domestic gerbils. In contrast, the non-injected CN of Tuvan gerbils showed no neuronal or spongiform degeneration with the ACS stain. We conclude that, in domestic gerbils, the naturally occurring spongiform lesions of the CN and the accompanying neurodegeneration are both results of a common mechanism, most probably excitotoxic.

Animals↗

Inhibition of nitric oxide synthase blocks osteoclastic bone resorption in adaptive bone modeling.

In this study, the auditory bulla of the gerbil was pressurized, leading to active modeling of the bone of the bulla wall with a significant increase in osteoclast surface and mineral apposition rate. Systemic infusion of L-N(G)-nitro-arginine-methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), inhibited this modeling process. The percentage osteoclast surface (Oc.S/BS) on the inner surface bulla wall was significantly reduced in the L-NAME-treated animals when compared with pressurized saline-treated bullae. Fluorescent bone surface (BSf) mineral apposition rates (MAR) and bone formation rate (BFR) were not significantly different in the pressurized bullae when the L-NAME group was compared with the control (vehicle only) group. However, L-NAME significantly suppressed BSf in the unpressurized bullae. Therefore, it is likely that nitric oxide is a mediator of osteoclastic resorption due to adaptive bone modeling through one or more of the isoforms of NOS.

Adaptation, Physiological↗

Kangaroo rats exhibit spongiform degeneration of the central auditory system similar to that found in gerbils.

Kangaroo rats develop spongiform degeneration of the central auditory system similar to that seen in the gerbil. Light microscopic and transmission electron microscopic study of the cochlear nucleus and auditory nerve root (ANR) of Dipodomys deserti and D. merriami show that spongiform lesions develop in dendrites and oligodendrocytes of the cochlear nucleus and in oligodendrocytes of the ANR that are morphologically indistinguishable from those extensively described in the Mongolian gerbil, Meriones unguiculatus. As in Mongolian gerbils, the spongiform degeneration in Dipodomys were much more numerous in animals continually exposed to modest levels of low-frequency noise (< 75 dB SPL). The kangaroo rats with extensive spongiform degeneration also show slightly, but significantly, elevated auditory brainstem evoked response (ABR) thresholds to low-frequency stimuli, a result also found in Mongolian gerbils. These results suggest that the elevated ABR thresholds may be the result of spongiform degeneration. Because low-frequency noise-induced spongiform degeneration has now been shown in the cochlear nucleus of animals from separate families of Rodentia (Heteromyidae and Muridae), the possibility should be investigated that similar noise-induced degenerative changes occur in the central auditory system of other mammals with good low-frequency hearing.

Acoustic Stimulation↗

Spongiform degeneration of the gerbil cochlear nucleus: an ultrastructural and immunohistochemical evaluation.

Observations from ultrastructural and immunohistochemical studies suggest that spongiform lesions in the gerbil cochlear nucleus are derived principally from dendrites. Almost one-fifth of the lesion profiles examined ultrastructurally exhibited synaptic contacts with axon terminals. In addition, approximately 80% of lesions are immunopositive for the dendrite-specific microtubule associated protein, MAP2. Ultrastructural studies showed a small percentage (8%) of lesions were derived from myelinated axons, although none were immunohistochemically labelled with antibodies to the tau protein. Staining with the astrocyte-specific markers GFAP, S-100 and vimentin yielded equivocal results, but did not support a major role for astrocytes in lesion formation. The histological profile matches that seen in some other well characterized types of spongiform degeneration.

Animals↗

Exposure to low frequency noise during rearing induces spongiform lesions in gerbil cochlear nucleus: high frequency exposure does not.

Spongiform lesions of the gerbil cochlear nucleus are reduced in number and extent by rearing in acoustic isolation compared with rearing while exposed to normal colony low-frequency background noise. This study tested whether rearing under exposure to noise bands of moderate intensity would increase the number and extent of cochlear nucleus spongiform lesions. Gerbils were reared from weaning to young adulthood in acoustic isolation chambers while continually exposed to moderately intense bands of either high frequency or low frequency noise. Exposure to low frequency noise resulted in lesion number and area densities that were more than twice those seen in gerbils exposed to high frequency noise. Lesion extent in the low frequency group was similar to that in colony-reared gerbils; lesion extent in the high frequency group was similar to gerbils reared in acoustic isolation. Comparisons within the posterior ventral cochlear nucleus revealed that the differences in lesion extent were most pronounced in the middle and dorsal-medial portions, the regions that are most responsive to middle and high frequencies. These finding suggest that the regional restriction of spongiform lesions within the cochlear nucleus does not have a tonotopic basis.

Acoustic Stimulation↗

Glial populations in the juvenile and adult Mongolian gerbil: relationship to spongiform degeneration of the ventral cochlear nucleus.

The gerbil cochlear nucleus is subject to a spongiform degeneration, the progression of which is dependent on auditory functional activity. The most affected region is the ventrolateral aspect of the caudal posterior ventral cochlear nucleus (PVCN). Lesion density and glial changes were quantified in this region for two age groups. Spongiform lesions increased significantly in area density from 4% in 60-day-old gerbils to 14% in 6-month-old gerbils. In spite of this significant increase in tissue damage, no gliosis was found. A significant age-related decrease in oligodendrocyte density was found in the PVCN.

Acoustic Stimulation↗

Incidence of otitis media in CBA/J and CBA/CaJ mice.

The inbred CBA/J mouse has become a standard experimental animal for auditory study because of its lifelong good hearing. In a newly established mouse breeding colony that housed CBA/J and CBA/CaJ mice to reared as auditory subjects, otitis media frequently afflicted CBA/J mice, reaching an incidence of 90% in animals greater than 400 days of age. Otitis media was not found in CBA/CaJ mice. Three attempts to establish a colony that was free of otitis were unsuccessful. Although the primary pathogen was not clearly established, Pasteurella pneumotropica was isolated from infected bullae. Partial control of otitis media followed the introduction of tetracycline prophylaxis. The CBA/CaJ mice may be suitable replacements for CBA/J mice in studies that require inbred mice with good hearing, since their auditory thresholds did not differ significantly from those of otitis-free CBA/J mice.

Animals↗

The mouse as a model for human audition. A review of the literature.

The mouse has several distinct advantages as an experimental model for human audition. Mice and humans express a similar presbyacusic and ototraumatic pattern. Several genetic mouse models also exist for conditions resembling human auditory disorders, such as otosclerosis. This paper reviews the strains of inbred mice (e.g. the CBA/J) which have recently been used as models for the normal human auditory system, describing their deficiencies. It is suggested that the F1 offspring of CBA/CaJ and AU/SsJ inbred mice would have advantages over existing models.

Acoustic Stimulation↗

Auditory brainstem function of the F1 offspring of the cross of CBA/CaJ and AU/SsJ inbred mice.

Inbred strains of laboratory mice have several distinct advantages as models for examining conditions that influence the human auditory system, but the CBA/J mouse which has most often been used as a normal model has recently been found to have several disadvantages. This paper is the first report of the auditory brainstem responses (ABRs) of the F1 offspring of CBA/CaJ and AU/SsJ parents. At midlife, high-frequency ABR thresholds are lower in the F1 than in either parental genotype. Tuning curves obtained by forward masking of the ABR also display heterosis, i.e. they are narrower in the F1 than in either parental strain.

Animals↗

Cochlear bone erosion: effects on cochlear hair cells. A scanning electron microscopy study.

Cochleae from gerbils with normal middle ears were compared with cochleae from gerbils with experimentally induced cholesteatomas that were in contact with the cochlear wall (stage III cholesteatomas). Cochleae from gerbils with stage III cholesteatomas were further divided into two groups: one without erosion of cochlear bone, and one with cholesteatoma-induced bone erosion but without cochlear fistulae. The cochleae with bone erosion showed significant loss of outer hair cells in the middle and apical turns, but not in the basal turn. The cochleae with stage III cholesteatomas but without bone erosion did not differ from normal controls. These results suggest that an ototoxic agent, involved in the process of bone erosion, acts through the bony cochlear wall.

Animals↗

Acoustic isolation reduces degeneration of the ventral cochlear nuclei in Mongolian gerbils.

The role of auditory experience in the development of spongiform degeneration in the cochlear nuclei of Mongolian gerbils was studied by comparing results of animals exposed to either high or low levels of ambient noise. Gerbils reared in a typical vivarium experienced higher levels of ambient noise than animals reared in acoustic isolation chambers. Animals reared in the colony room showed a much greater number density and area density of spongiform lesions in the CN than did gerbils reared in acoustic isolation. The differences in the number and extent of spongiform lesions between the two groups of gerbils appeared to reflect their differences in exposure to ambient noise. These differences in lesion number and extent were most pronounced in the tonotopic regions of the PVCN which correspond to the greatest differences in the spectral characteristics of the ambient noise to which the animals were exposed. These results were compared with results previously obtained from gerbils with loss of hearing experimentally induced by a conductive block or by sensorineural damage. The lesion numbers and extent reflected the auditory experience of each group; in descending order, colony-reared, isolate, conductive-block, sensorineural loss. These results strongly support the hypothesis that this gerbilline encephalopathy is directly related to auditory functional activity.

Animals↗

Effects of profound sensorineural loss on gerbilline auditory encephalopathy.

To investigate the role of acoustic stimulation in the development of spongiform degeneration in the cochlear nuclei of Mongolian gerbils, the right cochlea in 8 juvenile gerbils was chemically treated by placing sodium chloride (NaCl) crystals on the cochlear round window membrane. Sixty days after NaCl treatment there was extensive damage to the strial, sensorineural and supporting cells of the treated inner ear. The cochlear damage was accompanied by a dramatic decrease in the number and the extent of the spongioid lesions in the ipsilateral cochlear nuclei compared to the contralateral (control) cochlear nuclei. These results lend further support to the hypothesis that the progress of this disorder is related to auditory function.

Animals↗

Characteristics of auditory brainstem responses in ground squirrels.

Auditory brainstem responses (ABRs) were characterized at 37 degrees C in ground squirrels (Citellus lateralis) which were implanted with recording screws to record ABRs, and a thermistor to record brain temperature. After two weeks ground squirrels were reanesthetized and tone pips and clicks were delivered through a TDH-49 headphone. Recorded ABRs were found to vary in a predictable manner as a function of stimulus frequency and intensity. At intensities above 50 dB SPL, ABRs could be recorded over the range tested (2-32 kHz). An 8 kHz tone pip was the best frequency for recording ABRs at the lowest stimulus intensities. Latencies decreased as stimulus frequencies increased from 4 kHz to 32 kHz.

Acoustic Stimulation↗

Auditory brainstem responses in ground squirrels arousing from hibernation.

Auditory brainstem responses (ABRs) were recorded in ground squirrels (Citellus lateralis) arousing from hibernation. Squirrels implanted with recording screws to record ABRs, and a thermistor to record brain temperature, were placed in a cold room at 9 degrees C on a 2L:22D light-dark cycle. Hibernating animals were moved from the cold room and ABRs recorded during arousal. The responses showed a gradual development of all brainstem peaks. At low temperatures there were very long latencies to the peaks. The amplitudes of the peaks increased (with fluctuations) as brain temperature increased. The data indicate that neural generators on the brainstem auditory pathway were all activated early in arousal. These results do not support the hypothesis that successive peaks appear and grow in amplitude only after previous peaks are fully developed.

Acoustic Stimulation↗

Auditory experience affects degeneration of the ventral cochlear nucleus in Mongolian gerbils.

Gerbils exhibit a unique encephalopathy characterized by spongioform lesions in the neuropil of the cochlear nucleus and that others have recently described. The present results suggest that the course of this degenerative disorder is affected by acoustic experience. In gerbils in which acoustic stimulation was limited postnatally, the number and the extent of these lesions was dramatically reduced. Monaural deprivation reduced lesion number and extent only in the ipsilateral cochlear nucleus; binaural deprivation affected both cochlear nuclei. The lesions were most evident in certain portions of the cochlear nucleus, the caudal anterior ventral cochlear nucleus and the posterior ventral cochlear nucleus, sparing the rostral pole of the anterior ventral cochlear nucleus. In the affected regions the lesions were topologically restricted to the low and middle frequency regions. The apparent tonotopic distribution of lesions was associated with frequent exposure to low and middle frequency ambient noise.

Acoustic Stimulation↗

Bone resorption induced by middle-ear implants.

The pressure produced by expanding aural cholesteatomas has been implicated as a causal factor in the induction of osteoclastic resorption of adjoining bone. This concept is supported by observations of osteoclastic bone resorption produced by expansive tympanic implants. We induced osteoclastic bone resorption in gerbils with tympanic implants of autologous and homologous cartilage, silicone rubber, and Teflon, which exerted pressure only by forces of gravity and surface tension. We estimated that the pressure exerted by these implants ranged from 2.1 X 10(-3) to 8.0 X 10(-3) dynes/sq cm (1.6 to 6.0 mm Hg). These pressures are within the range of pressures known to be exerted by cholesteatomas.

Animals↗