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系統識別號 U0026-0812200914271275
論文名稱(中文) 水楊酸注射引發清醒大鼠的聽覺誘發電位改變
論文名稱(英文) Changes of auditory evoked potentials in conscious rats after daily salicylate injections
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 96
學期 2
出版年 97
研究生(中文) 萬怡伶
研究生(英文) I-lynn Wan
電子信箱 s3695108@mail.ncku.edu.tw
學號 s3695108
學位類別 碩士
語文別 英文
論文頁數 88頁
口試委員 口試委員-吳忠信
口試委員-曲在雯
指導教授-潘偉豐
口試委員-吳豐森
中文關鍵字 聽覺  水楊酸  耳鳴  大白鼠  誘發電位  大腦皮層 
英文關鍵字 tinnitus  auditory evoked potential  salicylate  cortex  rat 
學科別分類
中文摘要 耳鳴是沒有外界聲音傳入病人卻能感受到聲音存在的疾病。耳鳴是很普遍的聽覺疾病,不僅嚴重影響病人的日常生活可能導致憂鬱及自殺,形成當今嚴重的社會問題。目前為止,耳鳴產生的病理機制尚未明確也沒有效的治療方法。目前已知過量的水楊酸會引發人類的耳鳴,由行為實驗研究證實在動物身上也有相同效果。我們主要經由注射過量水楊酸在大白鼠體內誘發的耳鳴,藉由改變的聽覺誘發電位來研究耳鳴相關的形成機制。實驗方法於成鼠的聽覺皮質上植入低阻抗電極待大鼠手術傷口痊癒後,連續5天給予腹腔注射水楊酸(250mg/kg/day)並在注射3小時內紀錄其清醒狀況下聽覺誘發電位的變化。我們用不同的聲音刺激來誘發聽覺電位表現,包括single click、click trains 和不同音頻的tone bursts。實驗結果發現水楊酸會提高聽覺誘發電位反應的振幅以及降低其反應閾值。本實驗結果顯示經由窄譜(tone bursts)刺激引起的聽覺誘發電位反應比廣譜(click)刺激所產生的誘發電位更清晰且容易表現。實驗結果推測,大白鼠投予水楊酸藥物所誘發的耳鳴現象與聽覺過敏(hyperacusis)有相關性。總結,水楊酸藥物所誘發成鼠的耳鳴機制,可能經由水楊酸抑制周邊的聽覺接受區的活性,使得聽覺下行徑的傳導路徑活化,因而提高其聽覺誘發電位的增益值。
英文摘要 Tinnitus is the most prevalent hearing disorder and patients affected seriously may even commit suicide. Its patho-physiological mechanisms remain obscure and there is no effective cure for tinnitus to this day. Over-doses of salicylate (SA) are well-known to induce tinnitus in humans and behavioral evidence suggested similar effects in animals. Here we aimed to understand the underlying mechanisms of tinnitus by studying changes in auditory evoked potential (AEP) in animals receiving tinnitus-inducing doses of SA. Adult rats, after chronic implantation of epidural low impedance electrodes at the auditory cortex and full recovery from surgery, AEPs were recorded in the conscious state and results were analyzed for possible changes within 3 hours after SA injections (250 mg/kg/day, i.p.) for 5 consecutive days. A variety of sounds were used to evoke auditory potentials, including single click, click trains and tone bursts of various frequencies. Response changes were rather consistent across the 5 days and across animals. Average AEP integrals in the post- stimulus 28 ms were taken as response measure to tone bursts or clicks after SA treatment and in addition signs of loudness recruitment. SA invariably increased the response amplitude of averaged AEP to all sounds tested (p<0.001) and simultaneously reduced their response thresholds. Results were interpreted to reflect mainly cortical components of the hyperacusis associated with the SA-induced tinnitus. The changes in AEP to narrow band signals like tones are more easily interpreted than to broad band signals like clicks. Our finding of elevated gains in the AEP response-level function is consistent with a higher frequency-band activation of the auditory descending pathways, arising likely after SA-suppression of hearing sensitivity at the lower brainstem.
論文目次 Contents

Abstract..................................................I
Chinese Abstract........................................III
Contents.................................................IV
List of figures..........................................VI

1. Introduction...........................................1
1.1General background of tinnitus.........................1
1.2Pathophysiology of tinnitus............................2
1.2.1 Descending auditory system..........................3
1.3Tinnitus and hyperacusis ...............................4
1.4Salicylate animal model of tinnitus....................4
1.5Sites of SA actions....................................6
1.5.1 SA suppresses electro-motility of outer hair cells..6
1.5.2 SA elevates response threshold of auditory nerves...6
1.5.3 SA effects on cochlear nucleus .....................7
1.5.4 SA effects on superior olivary complex..............7
1.5.5 SA elevated sensitivity at the inferior colliculus..8
1.5.6 SA enhances neural activities of the auditory cortex9
1.6Auditory evoked potentials............................10
1.6.1 Cortical auditory evoked potentials.............10
1.6.2 Brainstem auditory evoked potentials ............11
1.7Aims of study.........................................12

2. Materials and Methods.................................13
2.1 Animal...............................................13
2.2 Recording electrode..................................13
2.3 Neurosurgery.........................................13
2.4 SA preparation and dosage............................14
2.5 Experimental paradigm................................15
2.6 Acoustic stimulation.................................15
2.7 Electrophysiological recording.......................16
2.8 Video monitoring of animal behavior..................16
2.9 Data analyses........................................17
2.9.1 AEP data pre-processing: rejection of outliers.....17
2.9.2 AEP data pre-processing: suppressing power-line interference.............................................17
2.9.3 Determining the AEP response-level function........18
2.9.4 Statistical analysis...............................18
2.10 Confirmation of recording...........................19

3. Results...............................................20
3.1 SA reduced response threshold to tone bursts.........20
3.2 SA elevated response amplitude to tone bursts........21
3.3 SA effects on AEP time waveform......................22
3.4 SA elevated tone burst BAER amplitude................23
3.5 SA increased AEP response gain to click and click train....................................................23
3.6 SA elevated BAER threshold to click and click train..23
3.7 Effect on recording sites on the AEP waveforms.......24
3.8 Individual statistics gain and threshold data........24

4. Discussion............................................25
4.1 Origins of AEP.......................................25
4.2 SA changed the auditory sensitivities................25
4.2.1 SA induced hyperacusis.............................27
4.2.2 Response differences between brainstem and cortex..28
4.3 SA induced changes to tones were frequency-dependent.28
4.4 SA induced changes to sounds were spectrum-dependent.29
4.5 Association cortical response suppressed by anesthesia..............................................30

5. Reference............................................31
APPENDICE...............................................79
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