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Biomedical subjects

B Canlon

Publications and source records attributed to B Canlon.

At least 37 records · Page 2Linked to original sources
PubMed1996

Protection of auditory neurons from aminoglycoside toxicity by neurotrophin-3.

Hearing is conveyed from the auditory receptors, the hair cells in the organ of Corti, to the brain via the spiral ganglion neurons. Damage or loss of either spiral ganglion neurons or hair cells causes hearing impairment. Such hearing disorders are often permanent and can be caused by therapeutic agents, such as aminoglycoside antibiotics and cisplatin, or by aging, loud sounds, infections and mechanical injury (1). Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), members of the neurotrohin family of neurotrophic factors that also include nerve growth factor (NGF) and neurotrophin-4/5 (NT-4), are important in development of the neuronal components of the inner ear. We report here that the loss of target innervation and the degeneration of approximately 90% of the adult spiral ganglion neurons caused by aminoglycoside toxicity can be prevented by infusion of the neurotrophic factor, neurotrophin-3 (NT-3) in the membranous labyrinth in guinea pigs. The potency of NT-3 in protecting spiral ganglion neurons from degenerating suggests that neurotrophins may be useful for the treatment of hearing disorders.

Aminoglycosides↗
PubMed1995

Protection against noise trauma by sound conditioning in the guinea pig appears not to be mediated by the middle ear muscles.

The aim of this study was to test whether the middle ear muscles (MEM) play a significant role in the phenomenon of sound conditioning in guinea pigs. After inducing a temporary threshold shift by noise exposure (2767 Hz tone, 103 dB SPL, 5 min), the magnitude and duration of loss, as well as the rate of recovery of the amplitude of the distortion product emission was determined at 1.75, 2.2, 2.8, and 3.5 kHz followed for 90 min post-exposure for (1) a sound conditioned group with intact MEM, and (2) a sound conditioned group with paralyzed MEM. Significant differences were not found for any of the distortion product parameters tested. The results suggest that the MEM do not significantly contribute to protection against noise trauma by sound conditioning.

Acoustic Stimulation↗
PubMed1995

Morphological and functional preservation of the outer hair cells from noise trauma by sound conditioning.

Guinea pigs were sound conditioned to a low-level, long-term pure tone stimulus (1 kHz, 81 dB SPL, 24 days) before exposure to a traumatic noise (1 kHz, 105 dB SPL, 72 h). Auditory brainstem response thresholds and distortion product otoacoustic emissions were obtained at selected frequencies before sound conditioning and at day 1, 5, 10, and 15 during sound conditioning as well as on the final 24th day. Auditory brainstem responses at 1 and 2 kHz were not affected at any time during sound conditioning. The amplitude of the distortion product otoacoustic emission showed minor alterations (below 10 dB) at selected frequencies only during the initial stages (day 1, 5, and 10) of sound conditioning in some, but not all the animals. Distortion product amplitudes were similar to control values on the 15th and 24th day of conditioning. Surface preparations of the organ of Corti did not reveal any significant hair cell loss induced by sound conditioning. The effect of a traumatic exposure (1 kHz, 105 dB SPL, 72 h) on a control group and a sound conditioned group was determined. The distortion product otoacoustic emission amplitude measured 4 weeks after the cessation of the traumatic exposure revealed significant differences. The amplitude of the distortion product otoacoustic emission for the control group was depressed at all tested frequencies and at lower frequencies (2.8, 2.1, and 1.75 kHz) the emissions did not show an increase in response to increases in intensity, of the primaries. The sound conditioned group showed increases in distortion product amplitude with increases in the intensity of the primaries for all tested frequencies and statistically significant reductions from the pre-exposure values were not found. Surface preparations from the control group indicated that the traumatic noise exposure affected nearly 100% of the outer hair cells around the 14 mm distance from the round window. The sound conditioned group showed a significantly less (50%) outer hair cell loss than the control group. The sound conditioned group illustrated an altered pattern of damage after subsequent noise trauma. There were two distinct regions of outer hair cell loss, one being around the 16 mm distance and the other around the 12 mm distance from the round window. These results imply that the intrinsic properties of the outer hair cells and/or the organ of Corti have been altered by sound conditioning.

Acoustic Stimulation↗
PubMed1995

The effect of noise trauma following training exposures in the mouse.

The effect of moderate level acoustic stimulation, or 'training', on a subsequent high intensity noise exposure was studied in CBA/Ca mice. Eight groups of mice were exposed to a variety of training paradigms as well as different intensity traumatic exposures. We sought a combination which would result in the maximum protective effect from acoustic trauma as measured by the auditory brainstem responses. Using a narrow band noise centered at 4.5 kHz, we investigated the effects of a 10-day 'interval' training regimen, allowing a rest period between successive training exposures, as well as several continuous training exposures. These training paradigms were followed by a 24 h traumatic noise exposure (also centered at 4.5 kHz) at one of three intensities, 107, 110, or 117 dB SPL which induce a temporary, a moderate, or a severe permanent threshold shift, respectively. In none of these trained groups was a protective effect demonstrated at any time up to one month following a subsequent traumatic noise exposure. Several groups demonstrated higher compound threshold shifts after the traumatic noise exposure compared to controls. After a recovery period of 4 weeks nearly all trained groups demonstrated a tendency toward higher permanent threshold shifts than the control, untrained, animals. While no protective effect was demonstrated, examination of the threshold shifts following the training periods and after the traumatic noise exposures raised interesting questions for future investigation regarding the inherent resistance to noise induced threshold shifts in the mouse.

Acoustic Stimulation↗
PubMed1994

Progressive hair cell loss induced by toluene exposure.

Rats were exposed to toluene by inhalation (1400 ppm, 16 h/d, 8 days) and sacrificed for morphological investigations at 3 and 5 days after the start of the exposure, and 4 days and 6 weeks after the end of the exposure. The cochleae were removed and prepared for light microscopy and scanning electron microscopy. After 3 days of toluene exposure no loss of hair cells was found. A slight loss in the third row outer hair cells was observed after 5 days of exposure. Four days after the 8-day long exposure a loss of hair cells was found in all 3 rows of outer hair cells, mainly in the middle and upper turns of the cochlea. Six weeks post-exposure the damage on the hair cells had progressed towards the basal part of the cochlea, and a 50-100% loss of outer hair cells together with some loss of inner hair cells were seen. A fairly good correlation was found between the frequency regions showing loss of hair cells and the threshold shifts previously measured by auditory brainstem responses and distortion product otoacoustic emissions in the same rats at corresponding times (Johnson and Canlon, 1994). These results indicate that the outer hair cells in the middle frequency region of the cochlea, were primarily affected by toluene exposure. However, after a long post-exposure period the damage extended basally and apically and some damage to the inner hair cells was seen.

Acoustic Stimulation↗
PubMed1994

Toluene exposure affects the functional activity of the outer hair cells.

Rats were exposed to toluene by inhalation (1400 ppm, 16 h/d, 8 days) and the auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOEs) were used as measures of the auditory sensitivity. These measurements were made before the exposure to toluene, 3 and 5 days after the start of the exposure and 4 days after the end of the exposure. To quantify the repeated DPOE data the area under the curve of the DPOE amplitudes versus the stimuli levels was calculated and used for statistical analysis. Results demonstrate that 3 days of toluene exposure tended to lower DPOE amplitudes and elevate ABR thresholds. Similarly after 5 days of exposure significantly lower DPOE amplitudes were observed at most frequencies along with elevated ABR thresholds. At 4 days post-exposure DPOE amplitudes were greatly diminished at all frequencies and the ABR thresholds were raised by about 40 dB between 1.6 and 20 kHz. These results show a parallel shift between ABR thresholds and DPOE amplitudes during toluene exposure. Furthermore, the results from the DPOE measurements indicate that mainly the outer hair cells are adversely affected by toluene exposure.

Administration, Inhalation↗
PubMed1993

Ultrastructural changes in the presynaptic region of outer hair cells after acoustic stimulation.

Protection against noise trauma results by sound-conditioning animals to a low-level, long-term acoustic stimulus prior to a damaging exposure. It is known that the outer hair cells are selectively protected by sound-conditioning. The aim of the present study was to determine if the intrinsic properties of the outer hair cell had been modified by sound-conditioning. A stimulus-related increase in the vesicle content in the presynaptic region was found. It is suggested that the outer hair cells are involved in sound conditioning and that changes in the presynaptic region can be one correlate to the protection against noise trauma by sound-conditioning.

Acoustic Stimulation↗
PubMed1993

Measures of auditory brain-stem responses, distortion product otoacoustic emissions, hair cell loss, and forward masked tuning curves in the waltzing guinea pig.

Measures of the auditory brain-stem response (ABR), distortion product otoacoustic emission (2f1-f2), hair cell loss, and forward masked tuning curves were obtained from waltzing guinea pigs and their age-matched controls at postnatal day 2, 9, 15, and 30. A mild ABR threshold shift (10-15 dB) is seen by 2 days postnatal and gradually increases to a more severe threshold shift (40-50 dB) by postnatal day 15. Already by 30 days the auditory brain-stem response, being beyond the output of the instrumentation, could not be elicited. The mean distortion product otoacoustic emission (DPOE) amplitude as a function of f1 amplitude for the postnatal day 2, 9, and 15 waltzing guinea pigs were only between 3 and 8 dB below the control values for stimulus levels below 65 dB SPL. The DPOE audiogram constructed for the waltzing guinea pigs shows no more than an 8-dB mean difference from the control values when the intensity of f1 was 50 dB SPL, and no more than 10 dB when f1 was 60 dB SPL. Analysis of the individual cases revealed that the DPOE amplitude could be greater than control values. On the contrary, when f1 stimulus levels were below 65 dB SPL, DPOEs could not be detected for the postnatal day 30 waltzing guinea pigs. At stimulus levels above 65 dB SPL, DPOEs could be recorded yet these responses were depressed from control values by 10 to 25 dB. Analysis of surface preparations of the organ of Corti from the day 15 waltzing guinea pig reveals that the prominent alteration occurs on the third row outer hair cells. To a lesser extent, the second row outer hair cells, and then the first row outer hair cells are affected while the inner hair cells appear normal. In contrast, the organ of Corti from the postnatal day 30 waltzing guinea pig showed a more extensive outer hair cell loss among all three rows as well as a considerable degree of inner hair cell loss. Forward masked auditory brain-stem response tuning curves were generated at 8, 4, and 1 kHz for control and waltzing guinea pigs between 2 and 12 days of age. All tuning curves obtained from waltzing guinea pigs showed progressive decreases in sensitivity with increasing age. The Q 10 dB values of the 1- and 4-kHz tuning curves were not different between the controls and the waltzing guinea pigs at any age.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗
PubMed1993

Dissociation between the calcium-induced and voltage-driven motility in cochlear outer hair cells from the waltzing guinea pig.

The waltzing guinea pig, possessing an hereditary progressive deafness, shows pathology to the actin-bearing structures within the hair cells of the organ of Corti. In particular, the affected structures include the stereocilia, the cuticular plate and, as shown in the present study, swollen and disorganized subsurface cisternae. To test whether this pathology affected outer hair cell motility, cells were isolated from waltzing guinea pigs and their age-matched controls and were subjected to either electrical or chemical stimulation. Visual detection thresholds and the magnitude of the electrically-induced length changes were equivalent for both groups. However, when intracellular calcium was increased with either the calcium ionophore, ionomycin or Ca2+/ATP (under permeabilized conditions with DMSO), length changes were significantly reduced for the outer hair cells from waltzing guinea pigs compared to the controls. The average percent length increase induced by 10 microM ionomycin for the outer hair cells from control animals was 2.3 +/- 1.7 whereas for postnatal day 4 waltzing guinea pigs it was 1.3 +/- 1.7. Postnatal day 7 and 10 waltzing guinea pigs responded with significantly smaller percent length changes. The intracellular concentration of ionic calcium increased similarly for both groups after the application of ionomycin as revealed with the indicator fluo-3. In the permeabilized cells in the presence of Ca2+/ATP, control cells responded with a percent length change of 3.5, whereas, age-matched waltzing outer hair cells responded with barely detectable length changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1992

Stage dependent development of intraocular cochlear grafts.

The intraocular grafting technique was employed to test whether the peripheral hearing organ, the cochlea, is capable of survival and an organized development in total isolation from the temporal bone. Rat cochleae obtained from gestation day 16, postnatal day 1 and 7 were chosen for transplantation into the anterior chamber of the eye of adult Sprague-Dawley rats. The grafts were maintained in the anterior chamber for 6, 10, or 15 weeks survival time. The salient features of this study is that 1) cochlear structures survive and, 2) the cochlear structures develop beyond their pre-grafted stage as determined from light and electron micrographs. In the present study, the grafts obtained at gestation day 16 (GD 16) and postnatal day 1 gave a much higher rate of survival and development than the postnatal day 7 grafts. In addition, grafts maintained for either 6 or 10 weeks had a better survival rate than those grafts left for 15 weeks. It is estimated from light and electron micrographs that the gestation day 16 otocysts that were maintained for 10 weeks, developed to the equivalent of a postnatal day 10 cochlea. The grafts obtained from postnatal day one rats developed to the equivalent of approximately 14 days after birth. Interestingly, in the absence of synaptic contact, the inner and outer hair cells were capable of survival, differentiation and maturation. It remains to be determined if the spiral ganglion cells require additional neurotrophic factors for survival in the anterior chamber of the eye.

Animals↗
PubMed1991

Mechanically induced length changes of isolated outer hair cells are metabolically dependent.

Isolated outer hair cells from the organ of Corti of the guinea pig have been shown to change length in response to a mechanical stimulus in the form of a tone burst at a fixed frequency of 200 Hz (Canlon et al., 1988). In the present study, the threshold of movement for individual outer hair cells is related to the original length of the cell such that long cells are more sensitive than short cells for all cochlear locations studied. Length changes could be elicited when the stimulus was projected at any site along the longitudinal axis of the plasma membrane. Length changes were not elicited when the stereocilia were stimulated directly. These mechanically-induced length changes were found to be metabolically dependent. In the presence of either sodium cyanide or 2,4-dinitrophenol, the motile response of outer hair cells was completely blocked within 30 min. When the extracellular pH was altered in a graded fashion, the motile response decreased gradually. Furthermore, 3 microM poly-L-lysine or poly-D-lysine of different molecular weights were also effective in blocking the motile response, whereas the negatively charged polyaminoacid, poly-L-aspartate, was not effective. Fluorescently-labelled poly-lysine demonstrated that the plasma membrane, stereocilia, and nucleus were the most intensely stained structures of the outer hair cells. It is suggested that the passive influx of poly-lysine is responsible for the inhibition of the motile response. Finally, the finding that the bidirectional motile response of isolated outer hair cells induced by mechanical stimulation is dependent on the metabolic state of the cell distinguishes this type of motility from the electrically induced outer hair cell shape changes.

2,4-Dinitrophenol↗
PubMed1989

Sound-induced motility of isolated cochlear outer hair cells is frequency-specific.

The inner ear is capable of highly selective frequency discrimination. This is achieved not only by the travelling wave of the basilar membrane in the cochlear partition, but also by the active participation of nonlinear and vulnerable elements that enhance frequency selectivity. It has been shown that isolated mammalian outer hair cells respond with a change in length when subjected to sound stimulation at a fixed frequency. Here we investigate the motile behaviour of isolated cells when the stimulus frequency is varied between 200 and 10,000 Hz. By varying the frequency and the intensity of the tone, it is possible to obtain 'tuning curves' for the motile response. We demonstrate that the cell body of solitary hair cells, free from contact with the basilar membrane, shows a sharply tuned motile behaviour. We suggest that frequency selectivity in the organ of Corti is amplified by the tuned motility of the cell body of outer hair cells.

Acoustic Stimulation↗
PubMed1988

Protection against noise trauma by pre-exposure to a low level acoustic stimulus.

Guinea pigs were pre-exposed to a low level acoustic stimulus prior to exposure to a stimulus known to yield a permanent threshold shift. This pre-treatment resulted in: 1) approximately a 20 dB reduction in the threshold shift relative to animals not pre-exposed, and 2) complete recovery from the threshold shift after 2 months.

Acoustic Stimulation↗
PubMed1988

Acoustic stimulation causes tonotopic alterations in the length of isolated outer hair cells from guinea pig hearing organ.

Isolated outer hair cells from the mammalian cochlea exhibit a motile response to electrical or chemical stimulation. Here we show that isolated outer hair cells can also respond to acoustic stimulation, in the form of a tone burst of 200 Hz, by either shortening or lengthening depending on their cochlear location. Cells from the apical region of the cochlea (long cells) responded by increasing their length, whereas those from more basal regions (short cells) responded by decreasing their length. Cells from intermediate positions showed an equal probability for either elongating or shortening. Both the elongating and shortening response was inhibited by 3 microM poly(L-lysine). It is suggested that this tonotopic and bidirectional acoustic response may be one of the active components underlying the specific phase and frequency displacement of the basilar membrane.

Acoustic Stimulation↗