Search PubMed⌕ Search

Biomedical subjects

J C Saunders

Publications and source records attributed to J C Saunders.

At least 55 records · Page 3Linked to original sources

The effect of acoustic overexposure on the tonotopic organization of the nucleus magnocellularis.

We assessed the effect a sound-induced cochlear lesion had on the tonotopic organization of the nucleus magnocellularis (NM) immediately after acoustic overexposure and following a twelve day recovery period. The acoustic overexposure was a 0.9 kHz tone at 120 dB sound pressure level (SPL) for 48 h. Initially after the acoustic overexposure, the tonotopic organization of the NM was statistically different from that of age-matched controls. Specifically, it appeared that the center frequencies of units in the frequency region of the NM associated with the acoustic overexposure had higher center frequencies than their control counterparts. Following a twelve day recovery period, when threshold sensitivity and frequency selectivity were operating normally, the tonotopic organization of the NM was not statistically different from age-matched controls. We suggest that the sound-induced changes in the tonotopic organization of the NM reflect peripheral damage in the basilar papilla. It has been well documented that similar exposure paradigms produce a loss of short hair cells and a degeneration of the tectorial membrane in the region of the basilar membrane associated with the overexposure. We postulate that the loss of these structures alters the micromechanics and tuning of the basilar membrane which is reflected in the observed changes in NM tonotopy. Following the recovery period, when those structures destroyed by the overexposure had regenerated and basilar membrane micromechanics were operating normally, the tonotopic organization of the NM returned to normal.

Acoustic Stimulation↗

Recovery of auditory structure and function in neonatal chicks exposed to intense sound for 8 days.

This paper describes hearing loss and recovery as well as cochlear damage in chicks, after a 200-h exposure to an intense pure tone, and compares the results to similar data following a 48-h exposure to the same sound. The results revealed that the magnitude of initial hearing loss and the rate of recovery were nearly the same for both exposures. The initial cochlear damage produced by the 200-h exposure, however, was less severe than that seen after the 48-h exposure. In addition, new hair cells were observed in the lesion area immediately after the 200-h exposure. However, after the 48-h exposure, they were first identified after several days of recovery. These observations were consistent with the conclusion that cochlear repair began during the longer exposure itself. The fact that hearing loss and recovery was the same for the two exposure conditions, while the level of cochlear damage differed, suggests that functional recovery depended on processes other than the regeneration or repair of hair cells and supporting cells. These other processes are considered.

Acoustic Stimulation↗

The effects of sound overexposure on the spectral response patterns of nucleus magnocellularis in the neonatal chick.

Spectral response plots from single cells in the chick nucleus magnocellularis were obtained following a 48 h exposure to a 0.9 kHz pure tone at 120 dB sound pressure level and after a recovery period of 12 days. Immediately after removal from the exposure, a variety of changes in the spectral response patterns of nucleus magnocellularis cells were noted. In particular, at recovery day 0, there was a significant decrease in spontaneous rate; a substantial loss of threshold sensitivity and frequency selectivity; and alterations in both the slope and dynamic range of the rate-intensity function. Interestingly, the maximum discharge rate appeared unaffected by the intense sound. Twelve days after removal from overstimulation, auditory function appeared to be operating at normal levels of efficacy as spontaneous rate, threshold sensitivity, frequency selectivity, and the dynamic range of the rate-intensity function were statistically identical to similar measures in nonexposed control birds. The loss and restoration of auditory function is correlated to structural damage and repair of the avian basilar papilla.

Acoustic Stimulation↗

The contribution of middle-ear sound conduction to auditory development.

1. This presentation summarizes recent research concerning the maturation of sound transmission through the middle-ear conducting system of various vertebrate species. 2. In this review the structural and functional aspects of middle-ear development are presented, as well as the relationships between these events. 3. Functional changes in middle-ear transmission demonstrated that the efficiency of sound conduction improved dramatically during the period of development. 4. The functional development of the middle ear was then compared with the maturation of auditory sensitivity measured from more central locations in the auditory system. 5. The results indicated that conductive development in some species determined the rate of sensitivity development. 6. These findings add an important dimension to our understanding of the underlying processes of hearing maturation.

Animals↗

Recovery of auditory function and structure in the chick after two intense pure tone exposures.

Groups of neonatal chicks were examined in three experimental conditions that differed in the age and number of times they were exposed to a pure tone of 0.9 kHz at 120 dB SPL for 48 h. Several animals were exposed once at 2 or 16 days of age, while others were subjected twice to the above stimulus, first at 2 days and then at 16 days. Evoked potential measures of threshold shift, obtained at 0, 12 or 26 days post-exposure, were used to determine the degree of hearing loss and recovery. The average threshold loss in the mid-range frequencies was about 57 dB at 0 days for all three conditions. This level was reduced to about 15 dB in all three groups at 12 days of recovery, while in birds exposed once at 2 days, but allowed 26 days to recover, the post-exposure thresholds returned to pre-exposure levels. Scanning electron microscopic analysis of cochlear structure was conducted in groups of similarly exposed and recovered animals. Twelve days post-exposure, the structural analysis revealed regeneration of a single honeycomb-like tectorial membrane layer in both the once and twice-exposed cochleae. However, damage to, and repair of, the tectorial membrane after the second exposure revealed the production of a second honeycomb layer in about half the animals examined. The results indicated that chicks retain the capacity to repair receptor epithelium damage and recover considerably from hearing loss after multiple exposures to intense sound.

Acoustic Stimulation↗

The growth of hearing loss in neonatal chicks exposed to intense pure tones.

One-day-old chicks were exposed to an intense pure tone (0.9 kHz, 120 dB SPL) and assigned to one of eight groups based on continuous exposure durations from 1 to 200 h. As each animal was removed from the exposure, it was anesthetized and an electrode was placed in the nucleus magnocellularis. Sound-evoked potentials were used to measure absolute thresholds and frequency selectivity. Thresholds were measured at 10 frequencies between 0.1 and 4.5 kHz while frequency selectivity was assessed by a simultaneous masking tuning-curve procedure at five probe-tone frequencies between 0.3 and 2.5 kHz. Threshold shift was greatest at 1.3 kHz and reached a maximum loss of approximately 57 dB between 48 and 200 h of exposure. The shape of the threshold-shift curve as a function of exposure duration (for frequencies between 0.9 and 2.5 KHz) suggested the presence of an early and late effect. The loss in tuning sharpness was evaluated by comparing the values of Q10 dB for control and exposed tuning curves and expressing the difference between them as a percent change. Probe-tone tuning curves above 0.9 kHz became less selective as exposure duration increased. A maximum decrease in tuning of about 54 percent was reached by 48 h and this remained constant to 200 h. The low-frequency tuning curves (below 0.9 kHz) did not show any systematic loss in selectivity. The changes in sensitivity and selectivity are discussed in relation to the patterns of cochlear injury that occurred on the basilar papilla as exposure duration lengthened.

Acoustic Stimulation↗

Differential regulation of transcription initiation from insulin-like growth factor-I (IGF-I) leader exons and of tissue IGF-I expression in response to changed growth hormone and nutritional status in sheep.

In the mammalian insulin-like growth factor-I (IGF-I) gene, exons 1 and 2 are differentially spliced to exon 3 producing alternate class 1 and class 2 transcripts. The aim of this study was to investigate the tissue expression of these leader exons in lambs growing at different rates as a result of chronic manipulation of nutritional and GH status. Riboprobes were developed so that leader exon-specific and total IGF-I gene expression could be determined using a single RNase protection assay. Lambs were fed a diet containing high or low protein content either ad libitum or at a restricted intake; within these dietary groups they were treated with either saline or GH for 10 weeks. Total hepatic IGF-I messenger RNA (mRNA) transcripts were significantly increased by GH (P = 0.004), protein (P = 0.002), and energy (P < 0.001) status as were circulating IGF-I concentrations (GH, P < 0.001; protein, P = 0.026; energy, P < 0.001). Exons 1 and 2 were expressed in liver but to a variable extent. Increased dietary energy and protein induced increased expression from both class 1 and 2 transcripts, but the percent increases was at least 5-fold greater for class 2 than for class 1 mRNA. GH treatment only stimulated significant increases in expression from class 2 transcripts. In the low protein, energy-restricted, saline-treated lambs exon 1 transcripts accounted for approximately 70% of total class 1 and 2 transcripts, and this proportion declined significantly as class 1 and 2 transcripts, and this proportion declined significantly as GH and nutritional status increased to only 30% in the high protein, ad libitum-fed, GH-treated animals; class 2 transcripts therefore displayed the opposite pattern of expression. These data indicate that exon 2 may be far more sensitive than exon 1 in intact animals which have been stimulated within normal physiological limits. Muscle IGF-I gene expression was at least 20-fold less than that for the liver and consisted mainly of class 1 transcripts. Muscle total IGF-I mRNA was insensitive to changed nutritional status or to GH treatment, even though significant increases in muscle growth occurred in response to ad libitum intake and GH, indicating that hepatically derived endocrine IGF-I could have a role in the regulation of muscle growth.

Animal Nutritional Physiological Phenomena↗

Insulin-like growth factor-II messenger ribonucleic acid expression in fetal tissues of the sheep during late gestation: effects of cortisol.

Using RNase protection analysis, insulin-like growth factor-II (IGF-II) mRNA levels were measured in various tissues from fetal sheep during late gestation (term, 146 +/- 2 days) and after experimental manipulation of fetal plasma cortisol levels. No gestational trend in IGF-II mRNA levels was observed in the fetal lung, kidney, or skeletal muscle. However, in the fetal liver, there was a marked decline in IGF-II mRNA abundance immediately before term, which closely paralleled the normal prepartum surge in fetal plasma cortisol. This decrease in hepatic IGF-II mRNA levels toward term was prevented when the cortisol surge was abolished by fetal adrenalectomy and was stimulated prematurely in fetuses younger than 130 days by exogenous infusion of cortisol. Hepatic and renal IGF-II mRNA abundances were also reduced when fetal cortisol levels were raised endogenously by maternal fasting in late gestation. Muscle IGF-II mRNA levels were reduced by fetal cortisol infusion, but not by maternal fasting, and were higher in adrenalectomized than in intact fetuses in late gestation. No change in IGF-II mRNA levels were observed in the fetal lung in response to altering the fetal cortisol level either exogenously or endogenously. When the data from all fetuses were combined regardless of treatment or gestational age, there was a significant inverse correlation between the plasma cortisol level in utero and IGF-II mRNA abundance in the fetal liver (P < 0.001), but not in any of the other fetal tissues studied. These findings show that cortisol suppresses IGF-II gene expression in the liver of the sheep fetus and indicate that the developmental change in hepatic IGF status toward term may be due to the prepartum cortisol surge.

Adrenal Glands↗

Growth of evoked potential amplitude in neonatal chicks exposed to intense sound.

The recovery of auditory function at selected intervals following exposure to a 0.9 kHz tone for 48 h at 120 dB SPL is described in neonatal chicks. Evoked potentials recorded from the nucleus magnocellularis were used to measure threshold sensitivity and peak-to-peak response amplitude as a function of stimulus intensity. The relation between evoked-response amplitude and stimulus intensity was nearly linear in control animals. However, at 10 days post exposure, the evoked response in mid-range frequencies showed a severe threshold shift and an abnormally rapid growth in amplitude. At 3 days post exposure, the rate of growth was nearly identical to that measured in control animals and threshold sensitivity showed considerable recovery. Current theories of amplitude-intensity growth and studies of basilar papilla damage and repair following intense sound exposure were applied in the analysis of these results.

Acoustic Stimulation↗

Middle-ear development: II. Morphometric changes in the conducting apparatus of the chick.

The ontogeny of various middle-ear structures was examined in 11 groups of chicks between 10 days embryonic and adult. Measurements of the tympanic membrane surface area and height, columella length, and that of the columella footplate, annular ligament, and oval window area were obtained using video micrographs and computer digitization techniques. The oval window matures first at 53 days post-hatching, whereas the columella achieves adult size at 74 days. The tympanic membrane surface area is the last middle-ear variable studied to reach adult size (79 days post-hatch). The columella increases its length from 0.63 mm (10 days embryonic) to 2.73 mm in the adult. The tympanic membrane area expands by 280% whereas the columellar footplate area increases by 11x. As a result, the pressure amplification of the middle ear due to the tympanic membrane/columellar footplate area ratio improves by over 400%. These data further contribute to our understanding of the functional development of the middle ear.

Animals↗

The structural and functional aspects of hair cell regeneration in the chick as a result of exposure to intense sound.

This paper summarizes the structural and functional damage caused by intense sound exposure in neonatal chicks. Scanning electron microscopy has been used to follow the structural changes to the papilla and their subsequent repair. Pure-tone exposures produced a localized lesion consisting of tectorial membrane destruction, changes in surface organization of the papilla, and hair cell loss. The papilla underwent significant repair following the exposure and new hair cells could be identified on the sensory surface after 4 days of recovery. In addition, various evoked-potential methods provided an objective assessment of auditory function and demonstrated that the peripheral ear was severely impaired by overstimulation. Auditory function returned to near normal levels within 3 days postexposure. The inescapable conclusion from these observations was that hair cell regeneration had little to do with the functional recovery observed during the first 3 days. Tectorial membrane regeneration and the restoration of cochlear micromechanics were combined to form a hypothesis to account for the restoration of auditory function.

Acoustic Stimulation↗

Middle ear development. I: Extra-stapedius response in the neonatal chick.

A laser interferometry system was used to study the ontogeny of tympanic membrane mechanical responses to sound as measured at the tip of the extra-stapedius (ES) in chicks. The ES velocity and phase responses in the frequency range between 0.2 and 10.0 kHz were measured in animals ranging from 3 days of age to adult. The slope of the low frequency response remained constant with age while the ES low frequency sensitivity increased by 11 dB. The sensitivity improvement indicated an increase in low frequency middle-ear admittance. However, there was no consistent developmental improvement in high frequency ES sensitivity. Comparisons between the growth of low frequency ES velocity, the development of admittance magnitude, and evoked potential threshold sensitivity developmental data indicated no clear relation between these measures.

Acoustic Stimulation↗

Stiffness of hair bundles in the chick cochlea.

The stiffness of hair bundles from isolated chick cochlear hair cells was measured in tissue culture medium. A water jet was used to deflect fiberglass fibers, quartz fibers, and hair bundles of isolated hair cells. A voltage-displacement curve was generated for a water jet ramp stimulus applied to miniature fiberglass and quartz fibers. Fiber displacements were measured using video image subtraction techniques. A force-voltage calibration curve was then derived for the fibers by modelling them as cantilever beams subjected to point forces at the tips. A voltage-displacement curve was then generated for isolated hair cell stereociliary bundles using the same procedure as for the fibers. A corresponding force-displacement curve was derived for isolated hair cells under water jet stimulation by correlating maximum ramp voltage from the hair cell's voltage-displacement curve to a corresponding force applied to a fiber from the fiberglass fiber calibration curve. The stiffness of the hair bundle, which is the slope of the hair cell's force-displacement curve, was then calculated using Hooke's law, assuming the force was distributed along the entire length of the hair bundle. The mean stiffness value was 5.04 +/- 2.68 x 10(-4) N/m for 14 hair cells, and was in close agreement with previously reported stiffness values of several investigators utilizing different animal models and procedures.

Animals↗

Middle ear development. III: Morphometric changes in the conducting apparatus of the Mongolian gerbil.

Middle-ear structural ontogeny was examined in 12 age groups of Mongolian gerbils between 2 and 42 days after birth. Measurements of tympanic membrane surface area; depth of the tympanic membrane cone; the lengths of the malleus and incus long processes; and stapes footplate, annular space, and oval window areas were obtained using video micrographs and computer digitization techniques. The incus long process matured first at 3.5 days after birth, while the pars flaccida surface area was the last middle-ear variable studied to reach adult size (26 days after birth). The incus long process increased its length by 30% from 0.5 mm to 0.65 mm. The malleus long process, however, demonstrated much more relative growth (47%). Pars tensa area expanded from 6.35 mm2 at two days after birth to its adult size of 16.9 mm2 and the stapes footplate expanded by 50%. The developmental changes observed in middle-ear anatomy are then discussed with regard to their contribution to the functional maturation of both the middle ear and more central auditory function.

Animals↗

Threshold shift, hair cell loss, and hair bundle stiffness following exposure to 120 and 125 dB pure tones in the neonatal chick.

One-day old chicks were exposed to one of two pure tone stimuli (0.9 kHz at 120 or 125 dB SPL) for 48 h. Three major results arose from a variety of tests that assessed the structural and functional consequences of the exposure on the peripheral auditory system at either 0 days or 12 to 15 days recovery. First, brainstem response data showed that the 120 and 125 dB groups had maximum evoked potential threshold shifts of 57 and 71 dB immediately after removal from the sound. Fifteen days post-exposure, the thresholds in the 120 dB group returned to near-normal levels, while in the 125 dB group, recovery was within 19 dB of control thresholds. Second, scanning electron microscopic measurements of hair cell density within the lesion showed that at 0 days recovery, the 120 and 125 dB groups had a 30% and 59% short hair cell loss, respectively, but by 15 days no differences could be identified between the exposed and control animals, regardless of exposure level. Finally, at 0 days of recovery, micromechanical stimulation data did not reveal any significant difference in stiffness between the control and surviving hair cells in the lesion area. Although the more intense exposure induced greater structural and functional damage in the chick cochlea, the birds retained or even enhanced their ability to replace lost hair cells and had partial hearing recovery by 15 days post-exposure.

Animals↗

The structural and functional consequences of acoustic injury in the cochlea and peripheral auditory system: a five year update.

This presentation considers important developments and new trends related to acoustic injury in the peripheral auditory system reported during the past 5 years. The discussion begins with the effect overstimulation has on the "active" cochlear process, and the associated loss in receptive field (tuning curve) selectivity. Exposure to intense sound also changes the structure and function of the tectorial membrane, sensory hair bundles, tip links, and intracellular organelles. All of these injuries may change the way in which energy is delivered to the transduction channels of the hair cell. Important new evidence describing the quantitative relation between hair cell loss and permanent hearing loss is reviewed, and the possibility that specific exposure conditions cause unique lesions to the inner or outer hair cells is explored. Finally, the importance of hair cell regeneration in the chick cochlea, changes in the CNS following acoustic injury, and the cochlear vascular system are considered.

Animals↗

The ovine insulin-like growth factor-I gene: characterization, expression and identification of a putative promoter.

Genomic DNA encoding the ovine insulin-like growth factor-I (IGF-I) gene was cloned and sequenced. The predicted amino acid sequence of the mature form of ovine IGF-I was highly homologous to that of human, rat and mouse. Analysis of the DNA sequence between exons 1 and 2 suggested the existence of an alternative 5' exon (exon 1A) and this was confirmed by polymerase chain reaction (PCR) analysis of sheep liver mRNA. Primer extension of mRNA from exon 1A indicated a class of transcripts which initiated at a point 32 nucleotides 5' to the Met codon of exon 1A to give a mRNA comprising exons 1A, 2, 3 and 5. In liver these transcripts co-existed with the alternative exon 1, 2, 3 and 5 mRNA form. Analysis by PCR of the 3' terminus of liver RNA indicated heterogeneity arising from multiple polyadenylation sites; however, of the two possible alternatively spliced 3' exons, only exon 5 could be detected. Expression of IGF-I mRNA, as measured by a solution hybridization/RNase protection assay, predominated in the liver of the neonate and the late-gestation fetus; however, lower levels of expression were seen in multiple tissues throughout fetal and neonatal development.

Amino Acid Sequence↗

Expression of a growth hormone-responsive exon of the ovine insulin-like growth factor-I gene.

The sheep insulin-like growth factor-I (IGF-I) gene encodes mRNAs containing three different 5'-untranslated sequences as a consequence of alternate splicing of leader exons. Using a combination of RNase protection and primer extension assays, we have mapped the transcriptional start sites of one of the leader exons, exon 1A. Transcription from exon 1A appeared to initiate from multiple points within a 20 bp region situated about 60 bp upstream of the exon 1A splice site. The presence of this transcript in the liver of animals treated with GH was enhanced five- to tenfold and contributed to about 95% of the total hepatic increase in IGF-I mRNA. This exon is generally expressed in a number of tissues immediately after birth; by about 4 weeks postpartum, however, expression is confined to liver. The regulation of hepatic and non-hepatic IGF-I synthesis by GH may involve different mechanisms.

Amino Acid Sequence↗