RESUMEN
Tinnitus is one of the leading disorders of hearing with no effective cure as its pathophysiological mechanisms remain unclear. While the sensitivity to sound is well-known to be affected, exactly how intensity coding per se is altered remains unclear. To address this issue, we used a salicylate-overdose animal model of tinnitus to measure auditory cortical evoked potentials at various stimulus levels, and analyzed on single-trial basis the response strength and its variance for the computation of the lower bound of Fisher information. Based on Fisher information profiles, we compared the precision or efficiency of intensity coding before and after salicylate-treatment. We found that after salicylate treatment, intensity coding was unexpectedly improved, rather than impaired. Also, the improvement varied in a sound-dependent way. The observed changes are likely due to some central compensatory mechanisms that are activated during tinnitus to bring out the full capacity of intensity coding which is expressed only in part under normal conditions.
Asunto(s)
Estimulación Acústica/métodos , Potenciales Evocados Auditivos , Almacenamiento y Recuperación de la Información/métodos , Percepción Sonora , Acúfeno/fisiopatología , Animales , Ratas , Ratas Sprague-Dawley , Salicilatos , Acúfeno/inducido químicamenteRESUMEN
Huntington disease (HD) is a degenerative disorder caused by expanded CAG repeats in exon 1 of the huntingtin gene (HTT). Patients with late-stage HD are known to have abnormal auditory processing, but the peripheral auditory functions of HD patients have yet to be thoroughly assessed. In this study, 19 HD patients (aged 40-59 years) were assessed for hearing impairment using pure-tone audiometry and assessment of auditory brainstem responses (ABRs). PTA thresholds were markedly elevated in HD patients. Consistent with this, elevated ABR thresholds were also detected in two mouse models of HD. Hearing loss thus appears to be an authentic symptom of HD. Immunohistochemical analyses demonstrated the presence of mutant huntingtin that formed intranuclear inclusions in the organ of Corti of HD mice, which might interfere with normal auditory function. Quantitative RT-PCR and Western blot analyses further revealed reduced expression of brain creatine kinase (CKB), a major enzyme responsible for ATP regeneration via the phosphocreatine-creatine kinase (PCr-CK) system, in the cochlea of HD mice. Treatment with creatine supplements ameliorated the hearing impairment of HD mice, suggesting that the impaired PCr-CK system in the cochlea of HD mice may contribute to their hearing impairment. These data also suggest that creatine may be useful for treating the hearing abnormalities of patients with HD.
Asunto(s)
Forma BB de la Creatina-Quinasa/genética , Pérdida Auditiva/enzimología , Pérdida Auditiva/genética , Enfermedad de Huntington/enzimología , Enfermedad de Huntington/genética , Adulto , Animales , Audiometría de Tonos Puros , Western Blotting , Estudios de Casos y Controles , Cóclea/efectos de los fármacos , Cóclea/enzimología , Creatina/farmacología , Modelos Animales de Enfermedad , Potenciales Evocados Auditivos del Tronco Encefálico , Femenino , Expresión Génica , Pérdida Auditiva/tratamiento farmacológico , Pérdida Auditiva/etiología , Humanos , Enfermedad de Huntington/complicaciones , Enfermedad de Huntington/fisiopatología , Masculino , Ratones , Ratones Transgénicos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Early sensory experience affects brain development. In rats, most somatic reflexes are not expressed at birth but may take as long as 2 weeks to emerge. Whether sensory enrichment during this early period affects reflex maturation remains unknown. Here, we exposed rat pups to a pure tone (4kHz, 65dB SPL, 8h/day) with their nursing mother during the first 3 postnatal weeks and measured the times when reflexes appeared on the basis of video recordings. Sound exposure accelerated by about 15% the appearance of all reflexes assessed (righting, cliff avoidance, vibrissa placing, negative geotaxis and auditory startle, p<0.001). In addition, sound exposure accelerated the appearance of developmental characteristics: incisor eruption, ear unfolding and eye opening. These changes occurred concomitantly with an increase in pups' body and brain weights, together with a dramatic increase in fluid intake of the nursing mother. These findings are the first evidence that early sound exposure, even before opening of ear canals, accelerates reflex development. We speculate that the observed changes could involve the nursing mother.
Asunto(s)
Percepción Auditiva , Reflejo , Estimulación Acústica , Animales , Animales Recién Nacidos , Tamaño Corporal , Peso Corporal , Encéfalo/anatomía & histología , Encéfalo/crecimiento & desarrollo , Conducta de Ingestión de Líquido , Conducta Alimentaria , Femenino , Masculino , Tamaño de los Órganos , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Grabación en Video , AguaRESUMEN
The peripheral-type benzodiazepine receptor (PBR), a putative receptor in Leydig cells, modulates steroidogenesis. Since benzodiazepines are commonly used in regional anesthesia, their peripheral effects need to be defined. Therefore, this study set out to investigate in vitro effects of the benzodiazepine midazolam (MDZ) on Leydig cell steroidogenesis, and the possible underlying mechanisms. The effects of MDZ on steroidogenesis in primary mouse Leydig cells and MA-10 Leydig tumor cells were determined by radioimmunoassay. PBR, P450scc, 3beta-HSD and StAR protein expression induced by MDZ was determined by Western blotting. Inhibitors of the signal transduction pathway and a MDZ antagonist were used to investigate the intracellular cascades activated by MDZ. In both cell types, MDZ-stimulated steroidogenesis in dose- and time-dependent manners, and induced the expression of PBR and StAR proteins, but had no effect on P450scc and 3beta-HSD expressions. Moreover, H89 (PKA inhibitor) and GF109203X (PKC inhibitor) attenuated MDZ-stimulated steroid production. Interestingly, the MDZ antagonist (flumazenil) did not decrease MDZ-induced steroid production in both cell types. These results highly indicated that MDZ-induced steroidogenesis in mouse Leydig cells via PKA and PKC pathways, along with the expression of PBR and StAR proteins. In addition, MDZ at high dosages induced rounding-up, membrane blebbing, and then death in MA-10 cells. In conclusion, midazolam could induce Leydig tumor cell steroidogenesis, and high dose of midazolam could induce apoptosis in Leydig tumor cells.
Asunto(s)
Anestésicos/toxicidad , Apoptosis/efectos de los fármacos , Células Intersticiales del Testículo/efectos de los fármacos , Midazolam/toxicidad , Esteroides/biosíntesis , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Flumazenil/farmacología , Expresión Génica/efectos de los fármacos , Indoles/farmacología , Isoquinolinas/farmacología , Células Intersticiales del Testículo/citología , Células Intersticiales del Testículo/metabolismo , Masculino , Maleimidas/farmacología , Ratones , Ratones Endogámicos C57BL , Proteína Quinasa C/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Sulfonamidas/farmacologíaRESUMEN
OBJECTIVE: To compare the complication rates of bowel perforation during colonoscopy performed with or without anesthesia. METHODS: We retrospectively analyzed 9501 case records of colonoscopy performed at the Chi Mei Medical Center between 2000 and 2004, and compared the rates of bowel perforation between patients receiving anesthesia during the procedure versus those that did not receive anesthesia. Poisson distribution was used for statistical analysis. RESULTS: Only one case of perforation was found in the non-anesthetized group (n = 2460) compared with two cases in the anesthetized group (n = 7041). No statistical difference was found (p = 0.6173; risk ratio = 0.6988; 95% confidence interval by Byar's method = 0.063-7.705). CONCLUSION: During colonoscopy, anesthesia per se does not affect the rate of bowel perforation.
Asunto(s)
Anestesia/efectos adversos , Colonoscopía/efectos adversos , Perforación Intestinal/epidemiología , Adulto , Anciano , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Prolonged sound exposure produces functional changes in the auditory neurons. It remains unclear whether such changes are detectable with morphometric measures like cell size. Here, after exposing juvenile rats (starting on week-4) to a monotone for 7 days, we measured the size of their cortical neurons. Neuronal profiles (nuclei and perikarya) in deep layers of the primary auditory cortex were digitized and measured on photomicrographs taken from 7 microm-thick histological sections stained with toluidine blue. To facilitate digitizing cell profiles, we used an image-analysis software that contains a confocal-like image-merging function to sharpen the edges. After sound exposure, both nuclei and perikarya expanded by about 1/3 in volume compared with controls (p<0.0001, Student's t-test). Such changes were not found in the visual cortex. Results showed that prolonged sound exposure increased the size of auditory neurons. Such activity-driven cell enlargement can be used as a simple measure to find other plastic changes in the brain.
Asunto(s)
Corteza Auditiva/citología , Neuronas/citología , Sonido , Animales , Tamaño de la Célula , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Acoustic stimulation is known to induce c-Fos expression in the auditory system but how the expression might be related to the time-variance of the sound (e.g., steady or frequency-varying) is unclear. Here we measured morphometrically Fos-immunohistochemical stains at the auditory brainstem after exposing rats to a pure tone or a narrow-range frequency modulated (FM) sound for various durations (10, 30 or 90 min). Nuclear sizes of Fos-stains at the cochlear nucleus (CN) and inferior colliculus (IC) were estimated under microscope. Tone stimulation at the given frequency (9 kHz) induced Fos-expression at locations consistent with the tonotopic maps, and no clear difference in the spatial distribution of the Fos-stains was observed across stimuli. In general, more Fos-stains appeared after longer stimulations and most notably cell nuclei labeled with Fos-immunoreactivity were statistically larger in size under longer pure tone and FM tone stimulations. Findings suggest that Fos-expression mechanisms are related to the selective response of different subpopulations of neurons to sounds of different time-varying properties. Results support that the time-variance of acoustic stimulation should be considered in the interpretation of Fos-expression findings.
Asunto(s)
Percepción Auditiva/fisiología , Núcleo Celular/metabolismo , Núcleo Coclear/metabolismo , Colículos Inferiores/metabolismo , Neuronas/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Estimulación Acústica , Animales , Vías Auditivas/citología , Vías Auditivas/metabolismo , Mapeo Encefálico , Núcleo Celular/ultraestructura , Tamaño de la Célula , Núcleo Coclear/citología , Inmunohistoquímica , Colículos Inferiores/citología , Neuronas/citología , Proteínas Proto-Oncogénicas c-fos/genética , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción/fisiología , Factores de TiempoRESUMEN
Pulmonary ventilation of patients implanted with a nasogastric tube is often difficult for medical personnel, since air leakage through the facemask and nasogastric tube interface is inevitable. Here we designed and tested a special facemask to improve ventilation in these patients. Forty patients with ASA class I-II were randomly assigned to two groups (study and control, n=20 each patients/group). All patients received abdominal surgery with a nasogastric tube inserted before operation. Before induction arterial lines were set up under local anesthesia. Blood gas samples were taken before, during and 1 min after endotracheal intubation. Haemodynamic data were obtained from the artery lines. Inspiratory and expiratory tidal volumes were measured by the Wright's spirometer connected to the anesthesia machine. For induction we used the new mask for the study group and the conventional mask for the controls. Blood gas values and leakage volumes were compared statistically (unpaired t-test, significant levels set at p<0.05). Air leakage was significantly reduced under the new mask with a concomitant improvement in PaO(2). There was however no change in terms of haemodynamic and PaCO(2) between the two groups. Results indicated the advantage of the new mask for patients with nasogastric tubes.
Asunto(s)
Intubación Gastrointestinal/métodos , Máscaras , Respiración Artificial/instrumentación , Diseño de Equipo , Análisis de Falla de EquipoRESUMEN
Sensitivity of central auditory neurons to frequency modulated (FM) sound is often characterized based on spectro-temporal receptive field (STRF), which is generated by spike-trigger averaging a random stimulus. Due to the inherent property of time variability in neural response, this method erroneously represents the response jitter as stimulus jitter in the STRF. To reveal the trigger features more clearly, we have implemented a method that minimizes this error. Neural spikes from the brainstem of urethane-anesthetized rats were first recorded in response to two sets of FM stimuli: (a) a random FM tone for the generation of STRF and (b) a family of linear FM ramps for the determination of FM 'trigger point'. Based on the first dataset, STRFs were generated using spike-trigger averaging. Individual modulating waveforms were then matched with respect to their mean waveform at time-windows of a systematically varied length. A stable or optimal variance time profile was found at a particular window length. At this optimal window length, we performed delay adjustments. A marked sharpening in the FM bands in the STRF was found. Results were consistent with the FM 'trigger point' as estimated by the linear FM ramps. We concluded that the present approach of adjusting response jitter was effective in delineating FM trigger features in the STRF.
Asunto(s)
Potenciales de Acción , Neuronas/fisiología , Animales , Ratas , Ratas Sprague-DawleyRESUMEN
Currently, the majority of neural stimulation studies are limited to acute animal experiments due to lack of suitable implantable microstimulation devices. As an initial step to observe the long-term effects of neural stimulation, a system consisting of an external wireless controller and an implantable dual-channel microcontroller-based microstimulator for tripolar high frequency blocking was developed. The system is not only small in size, and thus suitable for short-term implantation, but also has sufficient current output parameter ranges to meet the demand for high frequency blocking experiments. Using this implantable microstimulator, a series of experiments were conducted on New Zealand rabbit's tibial nerve, including frequency and amplitude selection in driving stimulus and blocking effect tests, which were designed to assess the feasibility and efficiency of the device via torque measurements. Our results showed that the implantable microstimulator system gave a satisfactory performance and could be utilized to achieve selective stimulation and blocking on various sizes of nerve fibers. Our implantable microstimulation system is not only a novel tool for neuromuscular control studies but could also provide a basis for developing various types of sophisticated neural prostheses.
Asunto(s)
Axones/fisiología , Electrónica Médica/instrumentación , Electrónica Médica/métodos , Bloqueo Nervioso/instrumentación , Bloqueo Nervioso/métodos , Animales , Estimulación Eléctrica/métodos , Electrodos Implantados , Masculino , Conejos , Nervio Tibial/fisiologíaRESUMEN
To simulate central auditory responses to complex sounds, a computational model was implemented. It consists of a multi-scale classification process, and an artificial neural network composed of two modules of finite impulse response (FIR) neural networks connected to a maximum network. Electrical activities of single auditory neurons were recorded at the rat midbrain in response to a repetitive pseudo-random frequency modulated (FM) sound. The multi-scale classification process divides the training dataset into either strong or weak response using a multiple-scale Gaussian filter that based on response probability. Two modules of FIR neural network are then independently trained to model the two types of responses. This caters for the possible differences in neuronal circuitry and transmission delay. Their outputs are connected to a maximum network to generate the final output. After training, we use a different set of FM responses collected from the same neuron to test the performance of the model. Two criteria are adopted for assessment. One measures the matching of the modeled output to the actual output on a point-to-point basis. Another measures the matching of bulk responses between the two. Results show that the proposed model predicts the responses of central auditory neurons satisfactorily.