臺灣博碩士論文加值系統

研究背景：電刺激被認為可以改善腦缺血大鼠的動作功能同時增加釋放神經再生時所需的生長因子，加速大腦修復的程度與速度。但是亦有學者認為急性期的電刺激介入之後，有可能會對缺血大腦造成反效果。本研究目的是在探討腦缺血急性期的電刺激對於大鼠動作功能以及梗塞體積的效果。
研究方法：本研究選用成年大鼠（公）接受中大腦動脈阻斷手術之後，隨機分配到電刺激組（n=9）與控制組（n=9）。兩組在中大腦動脈阻斷手術後24小時後開始接受為期七天的前肢電刺激介入，控制組的電刺激電源不會開啟。電刺激位置為患側前肢，刺激參數設定強度為3-5 mA，頻率是100Hz，每次三十分鐘，於氣體麻醉下進行。治療前後動作功能方面利用上爬桿（ladder climbing test）、平爬桿（parallel bar crossing test）與平爬格（fault foot placing）分別評估前後肢協調、後肢功能、與前肢功能。七天介入之後兩組皆會犧牲以進行2，3，5—氯化三苯基四氮唑染色，檢測大腦梗塞體積。本研究使用獨立t檢定分析實驗組與控制組間差異。
結果：電刺激組在上爬桿與平爬格測試中與控制組相比有顯著的進步。而在梗塞體積的測量中也可以看到電刺激組的梗塞體積顯著比控制組少。
討論：本研究結果顯示，患側前肢電刺激可以誘發急性期腦缺血大鼠的動作功能恢復，並且有效降低腦部梗塞體積。而動作功能恢復，特別是前肢功能，與腦部梗塞體積呈顯著相關，故本研究推測於患側前肢給予電刺激，可能藉由增加神經保護機轉，減少神經細胞持續死亡，進而改善急性期腦缺血的動作功能恢復。
結論：電刺激可以顯著降低腦部梗塞的體積，進而能改善中風大鼠的動作功能。

Background: Electrical stimulation (ES) is known to promote the recovery of motor function in rats with brain ischemia and to increase the expression of growth factors, which support neurogenesis in the brain. However, it is not known whether ES is beneficial or detrimental during acute brain ischemia. In this study, the ES effects on motor function and brain infarct volume after acute brain ischemia in rats were investigated.
Methods: Adult male Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO) first and were then randomly assigned to the ES group (n=9) and control group (n=9). The ES was administered to the forepaw under isoflurane anesthesia for 30 min per day for 7 days with the intensity of 3-5 mA and frequency of 100 Hz beginning 24 hours post MCAO procedure. The control group received the sham ES. The motor function was measured by ladder-climbing, parallel-bar-crossing, and foot-fault-placing test before and after completing the ES (or sham ES). Brain recovery was determined by infarct volume using 2,3,5-Triphenyl tetrazolium chloride (TTC) stain. Independent t test was used to analyze the difference between ES and control group. Significant level was set at 0.05.
Results: ES group demonstrated more improvement in ladder-climbing and foot-fault-placing test than the control group. The improvement in brain recovery as indicated by decrease of infarct volume was also significantly more than the control group.
Discussion: According to our results, ES can induce motor recovery together with the decrease in infarct volume in acute brain ischemic rats. In this study, we further noted that the infarct volume correlated significantly with the motor function especially the forelimb. Therefore, ES applied to forepaw may enhance the neuroprotection and thus decrease further neuronal death to result in motor function recovery.
Conclusion: The ES can reduce infarct volume and enhance motor functions in acute brain ischemic rats.

Contents.......................................................i
List of Tables & Figures.......................................................ii
誌謝.....................................................................................iii
中文摘要...............................................................................v
English Abstract..................................................................vi
Chapter I Introduction..........................................................1
1.1 Background..................................................................1
1.2 Treatment for stroke in acute stage.............................2
1.3 Sensorimotor stimulation during acute stage...............2
1.4 Objective and Hypothesis.............................................3
Chapter II Literature review.................................................4
2.1 Stroke pathophysiology in acute stage.......................4
2.2 Brain ischemia animal model: middle cerebral artery occlusion ............................................................................5
2.3 Sensorimotor stimulation after brain ischemia in acute phase ..........................................................................................6
2.3.1 Effects of peripheral functional electrical stimulation..7
2.3.2 Possible mechanisms for effects of electrical stimulation in brain ischemia....................................................................8
2.4 Summary........................................................................9
Chapter III Methods...............................................................10
3.1 Purpose and Hypothesis...............................................10
3.2 Animals..........................................................................10
3.3 Grouping ........................................................................10
3.4 Induction of Brain Ischemia.............................................11
3.5 Electrical Stimulation......................................................12
3.6 Motor Function Measurement.........................................12
3.6.1 Ladder-climbing...............................................................13
3.6.2 Parallel-bar-crossing.................................................13
3.6.3 Foot-fault-placing......................................................14
3.7 Infarct Volume Measurement .............................................14
3.8 Statistical Analysis ............................................................15
Chapter IV Results ...................................................................16
4.1 Infarct volume ..................................................................16
4.2 Motor function..................................................................16
Chapter V Discussion...............................................................18
5.1 Forelimb ES in acute phase of brain ischemia enhances brain recovery .................................................................................18
5.2 Forelimb ES in acute phase of brain ischemia induces motor function recovery ................................................................20
5.3 Effects of ES on brain activity after brain ischemia........22
5.4 Study limitations.............................................................23
Chapter VI Conclusion .........................................................24
References ........................................................................25
Appendix 1. Electrocorticogram (ECoG) technique................37

圖表目錄
Table 1. Basic information after MCAO procedure in ES and SC group....................................................................................30
Table 2. Motor function performance before (pre) and after (post) intervention in ES and SC group...........................................31
Figure 1. ES placement and rat position................................32
Figure 2. Illustration of the results of infarct areas in (a) ES group (b) SC group .......................................................................33
Figure 3. Brain infarct volume in ES group and SC group.....34
Figure 4. Motor function performance for ES and SC group..35
Figure 5. Brain activities demonstrated by ECoG. Pre-test: (a) Right S1FL (b) Left S1FL. Post-test: (c) Right S1FL (d) Left S1FL ..............................................................................................36

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