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系統識別號 U0026-0812200913591885
論文名稱(中文) 水楊酸在耳鳴的動物模式中對不同聲音誘發電位的影響
論文名稱(英文) Differential effects of salicylate on auditory evoked potentials in the tinnitus animal model
校院名稱 成功大學
系所名稱(中) 生理學研究所
系所名稱(英) Department of Physiology
學年度 95
學期 2
出版年 96
研究生(中文) 蘇育廷
研究生(英文) Yu-Ting Su
電子信箱 disp001@gmail.com
學號 s3692101
學位類別 碩士
語文別 英文
論文頁數 105頁
口試委員 指導教授-潘偉豐
口試委員-蕭富仁
口試委員-吳豐森
口試委員-陳贊如
中文關鍵字 水楊酸  誘發電位  耳鳴 
英文關鍵字 evoked potential  salicylate  tinnitus 
學科別分類
中文摘要 耳鳴是一種沒有外界聲音的時候感覺有聲音出現的現象,人類受試者報告出耳鳴的現象是高頻的聲音。 過量的水楊酸(阿斯匹靈的有效成分)已知可以在動物模式與人類受試者造成耳鳴。 之前的研究顯示水楊酸誘發耳鳴會造成高頻音域聽覺閾值上升 15分貝。 這種閾值上升的現象至今機制不明。了解耳鳴對於不同聲音的影響機制十分重要。 為了紀錄自由行動而且清醒動物的聽覺誘發電位,我們使用植入電極來記錄。 植入電極放在接近聽覺中腦下丘的位置。在注射連續注射五天水楊酸前後的誘發電位反應,改變不同聲音(純音刺激與廣譜變化的聲音)的刺激強度來記錄電位的改變。我們發現水楊酸注射對於廣譜變化的聲音造成聽覺誘發電位閾值上升,高頻純音刺激促進聽覺誘發電位反應,低頻純音刺激則沒有改變聽覺誘發電位反應。這是第一次在同一隻動物中發現到這種現象。我們解釋這種現象是歸因於不同的聲音刺激的特性及頻率組成所致。這個發現指出耳鳴的機制會涉及在高聲音刺激強度的時候開啟自主調節系統,低強度的聲音刺激強度則是由於水楊酸抑制耳蝸輸出所致。
英文摘要 Tinnitus is the phantom sensation of sound in the absence of the corresponding external stimuli. Multiple over-doses of salicylate (SA) induced reversible tinnitus in humans and animals. Previous studies showed that SA-induced tinnitus was associated with an elevated hearing threshold (of about 15 dB) especially affecting high frequency regions (~10-16 kHz). On the other hand, SA was also reported in amplification of auditory evoked potentials. Whether SA produces same effects to different sound stimuli remained unclear. This knowledge is important for the understanding of pathophysiological mechanism of tinnitus. Brainstem auditory evoked potential (BAEP) reflect the electrophysiological activity of large numbers of neurons in the brainstem auditory pathway with acoustic stimulation. Here, we recorded BAEP from intra-cranial electrodes chronically implanted in freely moving rats before and after daily doses of SA (250 mg/kg/day, i.p.) over a period of 5 consecutive days. In order to assess the SA effect on the auditory brainstem including the inferior colliculus, which presumably is involved in the genesis of tinnitus, the active epi-dural recording electrode was placed about inferior colliculus (2mm from lamda on one side), and the reference electrode at the bregma. Average BAEP integrals in the post-stimulus 10 ms were taken as the response measure to clicks or tone bursts of systemically varied intensities. We found an elevation of threshold (about 10 dB) of BAEP to clicks after SA treatment and in addition signs of loudness recruitment. But, the BAEP to tone bursts of 16 kHz was sensitized (about 10 dB) after the same SA treatment and in addition signs of hyperacusis. Such enhanced sensitivity was not obvious in the low frequency region of 4 kHz. This is the first time that a differential effect of SA on BAEP from different sounds was observed in the same animal. We explain that such differential effect could be related, among other factors, to the different threshold of BAEP to clicks and to tones, and to the difference in the frequency composition of acoustic stimuli. The present results suggested that the mechanisms of tinnitus could involve turning on the automatic gain control of the descending auditory system at higher intensity levels after SA suppresses the cochlear inputs at low intensity levels.
論文目次 Abstract (Chinese)..........................3
Abstract ..............................4
Acknowledge (Chinese) ........................ 5
Contents...............................6
List of figures............................8

1. INTRODUCTION
1.1 Tinnitus and its pathophysiological mechanisms...........10
1.2 Tinnitus animal models and salicylate (SA) effects on the auditory system.12
1.2.1 SA reduces the electromotility of outer hair cells.........13
1.2.2 SA elevates threshold in an auditory nerve...........14
1.2.3 SA effects on cochlear nucleus................15
1.2.4 SA effects on superior olivary nucleus.............16
1.2.5 SA increases neural activity of the inferior colliculus.......17
1.2.6 SA enhances neural activities of the auditory cortex.......18
1.3 Brainstem auditory evoked potential (BAEP) ...........18
1.4 Aims of study........................20

2. MATERIALS AND METHODS
2.1 Chronic animal preparation...................21
2.2 SA injections and recording paradigm...............22
2.3 Electrophysiological recordings.................23
2.4 Acoustic stimuli........................23
2.5 Video recordings of animal movements..............24
2.6 Data analyses.........................25
2.6.1 Video analysis of animal movements..............25
2.6.2 BAEP data pre-processing: rejection of over-sized trials......25
2.6.3 BAEP response intensity functions..............27

3. RESULTS
3.1 SA elevated click BAEP threshold................28
3.2 Time profiles of SA effects on click BAEP.............29
3.3 SA enhanced 16 kHz tone burst BAEP...............30
3.4 SA did not alter 4 kHz tone burst BAEP..............30


4. DISCUSSION
4.1 Origins of the BAEP......................31
4.2 SA enhanced 16 kHz but not 4 kHz BAEP.............32
4.3 Dynamic range was compressed in click BAEP...........33
4.4 Possible involvements of automatic gain control in SA effects on BAEP.34

5. REFERENCES.........................36

6. APPENDICES
Appendix Ⅰ Acoustic calibration of the sound delivering system.....67
Appendix Ⅱ Matlab programs of data analysis............68
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