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研究生(外文):Hsing-Hui Su
論文名稱(外文):Effects of Middle Cerebral Artery Occlusion on Cardiac Autonomic Function and Sleep Pattern in Freely Moving Male, Female and Ovariectomized Rats
指導教授(外文):Cheryl C. H. Yang
外文關鍵詞:strokemiddle cerebral artery occlusionestrogenautonomic functionparasympathetic activitysleep
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背景:中風慢性期之後,對自主神經功能與睡眠是否有影響,目前研究尚未有定論。我們希望藉由具可良好控制一致性之中大腦動脈梗塞 (MCAO) 的動物模式,並結合無線多頻道生理紀錄系統及睡眠與HRV分析技術,來觀察MCAO之後,對睡眠與自主神經功能的影響。此外,動情素對心血管疾病,自主神經與睡眠的影響也分別有不同的研究報告過其正面作用。因此第二部份,我們將探討去卵巢雌鼠在中風後給予動情素對其梗塞體積、自主神經功能與睡眠是否具改善效果。
材料與方法:實驗使用同周齡雄性與雌性Wistar-Kyoto大鼠 (WKY),雌鼠分為三組:正常雌鼠 (偽去卵巢)、去卵巢以及去卵巢並於MCAO後外給雌激素。首先植入腦波、心電與肌電之電極,用來記錄EEG, EMG及ECG, 其中EEG可得腦波活性,EEG及EMG作為睡眠分析判讀和ECG訊號作為心率變異性頻譜分析來源。電極植入後7-10日,動物隨機分派作MCAO或偽MCAO手術。之後追蹤四周長期變化,每周記錄一次生理訊號。
結果:與偽MCAO比,MCAO除了確實造成明顯腦梗塞,也明顯造成慢性24小時的安靜睡眠總量減少,平均心率變異性之高頻 HF (副交感神經活性指標) 下降。區別光亮與光暗周期可見上述現象在光暗時特別明顯,並且也改變其睡眠品質。這種現象主要發生在MCAO後一至三周。三組雌鼠在MCAO後,都確實造成明顯腦梗塞 但補充動情素者似乎有較少的梗塞範圍,然而睡眠參數並未受到明顯影響。而在MCAO後給予動情素的去卵巢雌鼠,與去卵巢組比較,可見其副交感強度上升。比較三組雌鼠MCAO後損傷側腦波各頻帶的功率亦發現給予動情激素後可改善其表現。

Background and Purpose-The Chronic autonomic function and sleep architecture changes in patients post-stroke were not fully conclusion. Using a well-controlled middle cerebral artery occlusion (MCAO) model, together with wireless polysomongraphic recordings and the techniques of sleep and heart rate variability analysis, this study aimed to investigate the long-term effects on sleep patterns and autonomic function in free moving rats after MCAO. As Estrogen to cardiovascular disease, there are different results of positive effects on autonomic system and sleeping respectively. Therefore when looking into second part, we will discuss whether there will be any improvement effect on autonomic system or sleeping of estrogen on post-stroke female ovariectomized rat.
Methods-Male and female Wistar-Kyoto rats (WKY) were usesd in this study. And the female rats were divided into three groups: sham-ovariectomized (Female), ovariectomized (OVX), and ovarian removed with estrogen therapy (OVX+E). First, all animals were implanted with electrodes to wirelessly record electroencephalogram (EEG), electromyogram (EMG) and electrocardiogram (ECG) information, which then were used to analyze sleep patterns and heart rate variability (HRV). After 7-10 days, the rats were divided into two groups; one group underwent MCAO surgery, while the other group underwent sham surgery. Then, the HRV, sleep patterns and EEG frequency power of these groups were compared over the following 4 weeks.
Results-Compared with sham-MCAO group, the MCAO significantly decreased accumulated quiet sleep (QS) time over 24 h during the third week. The percentage of QS time, average duration of the QS stage and the delta power of the EEG were also significantly decreased in MCAO group during the dark period. In addition, the high frequency power of the HRV (an index of cardiac vagal activity) during active waking and paradoxical sleep were significantly suppressed during the first to third weeks after MCAO. The female, OVX, and OVX+E got the significant brain infarction after MCAO, and the infarction volume of OVX+E seems smaller than the others. Hoever, the sleep time% of female, OVX, and OVX+E were not influenced significantly between each other. HF of HRV after MCAO was higher in the OVX+E group than in OVX. And the EEG performance in OVX+E group was also better than the other two groups.
Conclusions-This study showed that the long-term effects of ischemic stroke injury involve significant changes to the rats’ sleep/wake patterns, including decreased QS time and changed autonomic functioning so that there is impaired cardiac vagal activity after MCAO. The second part experiment, suggest that estrogen could partially improving vagal function and neuron function after MCAO. But it still needs more researches to confirm.

Signature Page i
Thesis Approval Form ii
Acknowledgments iii
Chinese Abstract iv
English Abstract vi
Contents viii
List of Figures and Tables x
Introduction 1
Materials and Methods 4
Results 11
Discussion 16
Tables 23
Figures 26
References 37

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