Biomedical subjects

Carol A Bauer

Publications and source records attributed to Carol A Bauer.

9 recordsLinked to original sources

PubMed2007

Vigabatrin, a GABA transaminase inhibitor, reversibly eliminates tinnitus in an animal model.

Animal models have facilitated basic neuroscience research investigating the pathophysiology of tinnitus. It has been hypothesized that partial deafferentation produces a loss of tonic inhibition in the auditory system that may lead to inappropriate neuroplastic changes eventually expressed as tinnitus. The pathological down-regulation of gamma-amino butyric acid (GABA) provides a potential mechanism for this loss of inhibition. Using an animal model previously demonstrated to be sensitive to treatments that either induce or attenuate tinnitus, the present study examined the effect of the specific GABA agonist vigabatrin on chronic tinnitus. It was hypothesized that vigabatrin would decrease the evidence of tinnitus by restoring central inhibitory function through increased GABA availability. Vigabatrin has been demonstrated to elevate central GABA levels (Mattson et al. 1995). Tinnitus was induced in rats using a single 1-h unilateral exposure to band-limited noise, which preserved normal hearing in one ear. Psychophysical evidence of tinnitus was obtained using a free-operant conditioned-suppression method: Rats lever-pressed for food pellets and were trained to discriminate between the presence and absence of sound by punishing lever pressing with a mild foot shock (0.5 mA; 1 s) at the conclusion of randomly introduced silent periods (60 s) inserted into background low-level noise. Additional random insertion of pure tone and noise periods of variable intensity enabled the derivation of psychophysical functions that reflected the presence of tinnitus with features similar to 20-kHz tones. Vigabatrin was chronically administered via drinking water at 30 and 81 mg kg-1 day-1, with each dose level tested over 2 weeks, followed by a 0-mg washout test. Vigabatrin completely and reversibly eliminated the psychophysical evidence of tinnitus at both doses. Although vigabatrin has serious negative side effects that have prevented its clinical use in the USA, it is nevertheless a potentially useful tool in unraveling tinnitus pathophysiology.

4-Aminobutyrate Transaminase↗

PubMed2007

Noise in animal facilities: why it matters.

Environmental noise can alter endocrine, reproductive and cardiovascular function, disturb sleep/wake cycles, and can mask normal communication between animals. These outcomes indicate that noise in the animal facility might have wide-ranging affects on animals, making what laboratory animals hear of consequence for all those who use animals in research, not just the hearing researcher. Given the wide-ranging effects of noise on laboratory animals, routine monitoring of noise in animal facilities would provide important information on the nature and stability of the animal environment. This special issue will highlight the need for more thorough monitoring and will serve as an introduction to noise and its various effects on animals.

Animals↗

PubMed2006

Gap detection deficits in rats with tinnitus: a potential novel screening tool.

The study describes a novel method for tinnitus screening in rats by use of gap detection reflex procedures. The authors hypothesized that if a background acoustic signal was qualitatively similar to the rat's tinnitus, poorer detection of a silent gap in the background would be expected. Rats with prior evidence of tinnitus at 10 kHz (n = 14) exhibited significantly worse gap detection than controls (n = 13) when the gap was embedded in a background similar to their tinnitus. No differences between tinnitus and control rats were found with 16 kHz or broadband noise backgrounds, which helped to rule out explanations related to hearing loss or general performance deficits. The results suggest that gap detection reflex procedures might be effective for rapid tinnitus screening in rats.

Animals↗

PubMed2006

Effect of gabapentin on the sensation and impact of tinnitus.

OBJECTIVES/HYPOTHESIS: This study evaluated the effectiveness of gabapentin in treating chronic tinnitus in two populations: participants with tinnitus with associated acoustic trauma and participants with tinnitus without associated acoustic trauma. The hypothesis was that gabapentin would decrease both subjective and objective features of tinnitus in the trauma group but would be less effective in the nontrauma group. STUDY DESIGN: Prospective, placebo-controlled, single-blind clinical trial. METHODS: Pure-tone audiograms and personal histories were used to categorize tinnitus etiology as either secondary to acoustic trauma or not associated with acoustic trauma. Participants were restricted to those with moderate to severe tinnitus for at least 1 year. All participants received gabapentin in a graduated ascending-descending dose series extending over 20 weeks (peak dose of 2,400 mg/d). RESULTS: There was a significant improvement in tinnitus annoyance for the trauma group (P = .05). Other subjective aspects of tinnitus were not significantly affected in either group. Between-subject variability of therapeutic response was considerable. Nevertheless, in consideration of subjective loudness ratings, 4 of 19 nontrauma participants and 6 of 20 trauma participants showed an improvement of 20% or better. In consideration of psychoacoustic loudness estimates, 3 of 19 nontrauma and 6 of 20 trauma participants showed an improvement of 20 dB HL or greater. Evenly dividing each group into high and low responders revealed significant improvement in loudness at 1,800 and 2,400 mg/day for the trauma high-response subgroup (P = .007). No significant improvement was obtained for other subgroups. CONCLUSION: Gabapentin is effective in reducing subjective and objective aspects of tinnitus in some individuals, with the best therapeutic response obtained in individuals with associated acoustic trauma.

Adolescent↗

PubMed2005

Marking multi-channel silicon-substrate electrode recording sites using radiofrequency lesions.

Silicon-substrate multi-channel electrodes (multiprobes) have proven useful in a variety of electrophysiological tasks. When using multiprobes it is often useful to identify the site of each channel, e.g., when recording single-unit activity from a heterogeneous structure. Lesion marking of electrode sites has been used for many years. Electrolytic, or direct current (DC) lesions, have been used successfully to mark multiprobe sites in rat hippocampus [Townsend G, Peloquin P, Kloosterman F, Hetke JF, Leung LS. Recording and marking with silicon multichannel electrodes. Brain Res Brain Res Protoc 2002;9:122-9]. The present method used radio-frequency (rf) lesions to distinctly mark each of the 16 recording sites of 16-channel linear array multiprobes, in chinchilla inferior colliculus. A commercial radio-frequency lesioner was used as the current source, in conjunction with custom connectors adapted to the multiprobe configuration. In vitro bench testing was used to establish current-voltage-time parameters, as well as to check multiprobe integrity and radio-frequency performance. In in vivo application, visualization of individual-channel multiprobe recording sites was clear in 21 out of 33 sets of collicular serial-sections (i.e., probe tracks) obtained from acute experimental subjects, i.e., maximum post-lesion survival time of 2h. Advantages of the rf method include well-documented methods of in vitro calibration as well as low impact on probe integrity. The rf method of marking individual-channel sites should be useful in a variety of applications.

Animals↗

PubMed2005

Cochlear structure and function after round window application of ototoxins.

Topical round window application of ototoxic agents has been a useful method for studying ototoxicity and hearing loss in the mammalian cochlea. For example, species-specific differences in cochlear susceptibility to damage have been documented using this technique. Carboplatin has been characterized in the literature as a selective inner hair cell (IHC) toxin in chinchillas, while cisplatin has been characterized as a selective outer hair cell (OHC) toxin. The present experiment quantified dose-dependent damage to cochlear hair cells in the chinchilla after a single direct round window application of either cisplatin or carboplatin. Detailed cytocochleograms were obtained for the entire cochlear duct, for a range of doses, along with auditory brainstem response thresholds. In agreement with the literature, although there was variability, at the lowest concentrations tested (2 and 3 mg/ml), carboplatin produced substantial IHC damage with no OHC damage. In contrast, the effects of cisplatin were more variable, and contrary to published reports, across the range of doses producing OHC damage, IHC damage was always observed. Limitations of direct round window ototoxin treatments are discussed, in addition to their potential application in the study of tinnitus.

Animals↗

PubMed2005

The effect of dorsal cochlear nucleus ablation on tinnitus in rats.

A growing body of evidence implies that the dorsal cochlear nucleus (DCN) plays an important role in tinnitus. To test the hypothesis that the rostral output of the DCN is necessary for the experience of chronic tinnitus, the dorsal DCN and the dorsal acoustic stria of rats with psychophysical evidence of tinnitus was ablated. If the DCN plays a necessary role in the generation of chronic tinnitus, ablating the DCN should decrease the evidence of tinnitus in subjects previously shown to have tinnitus. Contrary to prediction, bilateral dorsal DCN ablation did not significantly (n=11, p=0.707) affect the psychophysical evidence of tinnitus, and ipsilateral dorsal DCN ablation appeared to increase the evidence of tinnitus (n=9, p=0.018) compared to pre-ablation performance. It was concluded that the DCN does not act as a simple feed-forward source of chronic tinnitus. Alternative hypotheses were considered, among them that elevated DCN activity following acoustic trauma triggers persistent pathological changes distributed across more than one level of the auditory system. In addition to serving as a trigger, the DCN may also modify the experience of tinnitus, since the evidence of tinnitus was enhanced by ipsilateral DCN ablation.

Acoustic Stimulation↗

PubMed2004

Mechanisms of tinnitus generation.

PURPOSE OF REVIEW: The current understanding of mechanisms of tinnitus generation is continuing to advance. This review is intended to outline new knowledge in the areas of neuroanatomy, physiology, psychophysics, and brain imaging that are revealing novel mechanisms of tinnitus development. Advances in these areas will open new avenues for effective treatment of tinnitus. RECENT FINDINGS: Application of high-pulse train electrical stimulation to the cochlea may be effective in restoring the normal pattern of spontaneous activity from the periphery that is interpreted by the auditory brainstem as coding for silence. Clinical and laboratory evidence for a significant interaction between the somatosensory and auditory systems has important implications for understanding and treating tinnitus. Application of principles of neuroplasticity and novel imaging techniques has expanded our understanding of tinnitus through analogous approaches to phantom limb pain. Finally, a novel receptor type recently located in auditory neurovascular structures has opened a new field of study of inflammatory mechanisms contributing to tinnitus. SUMMARY: Our understanding of the mechanisms that lead to a phantom auditory perception, and the associated debilitating consequences of this sensory experience, is continuing to improve. Tinnitus appears to be significantly affected in complex ways by somatosensory, limbic, and motor influences. Effective treatments will certainly emerge from these new areas of research.

Acoustic Stimulation↗

PubMed2003

Animal models of tinnitus.

Tinnitus is a complex phenomenon that is poorly understood. A significant tool for studying the pathophysiology of tinnitus and exploring potential treatments is an animal model. This article discusses the general techniques for evaluating psychophysical phenomenon in nonhuman subjects. An overview of a model of chronic tinnitus in rats and chinchillas is presented.

Animals↗