- 學位論文
腦損傷鼠模式下探討中樞神經電刺激對於膀胱功能影響
Effect of Neuromodulation with Deep Brain Stimulation on Bladder Function in Traumatic Brain Injury Rats
摘要
根據2012年衛福部統計，事故傷害名列台灣十大死因之一，其中創傷性腦損傷約占兩成左右。隨著醫療技術進步，存活率顯著提升，但大部分患者因為腦組織永久損壞，常造成運動、感覺、與泌尿系統等終生障礙，而慢性排尿障礙將有可能導致尿道感染、尿失禁，嚴重甚至引發腎衰竭而致死。因此，排尿障礙的病患是不容忽視的問題。 在臨床治療上，中樞神經損傷所造成的生理功能障礙，目前仍無任何方便又有效的治療方式。過去文獻顯示，深腦電刺激除了對於巴金森氏患者的動作控制產生明顯改善之外，對於病患的感覺功能缺失也有明顯的治療效果。因此，深腦電刺激調控應是一種新的替代的新治療發展方向。然而，目前為止，深腦電刺激對於膀胱調控之生理機制以及治療效果尚未清楚。若選擇電刺激治療下泌尿道排尿功能障礙，偵測膀胱狀態進而在適當的時間點進行電刺激就顯得相當重要。目前臨床上是以尿道動力學檢查來偵測膀胱狀態，如利用體外超音波量測膀胱體積，或是尿道插管量測膀胱內壓；但體外超音波無法對電刺激調控即時回饋，而尿道插管會對於病患的造成不適感。本研究希望以外尿道括約肌肌電圖做為即時偵測膀胱狀態之依據，此方法能將病患的不適感降到最低，且能夠達到即時回饋。因此，本研究希望建立一套再現性高的腦損傷大白鼠動物模型，透過自製電刺激系統，以外尿道括約肌肌電圖作為回饋訊號即時偵測膀胱狀態之依據，建立一套即時偵測膀胱狀態的系統，並將此系統應用於腦損傷大白鼠進行試驗，觀察其膀胱功能之修復情形，以解決腦損傷鼠尿液滯留的問題。 實驗結果統計，腦損傷動物模型之實驗再現性達71%，此模型有助於定量腦損傷後的膀胱功能，比較正常鼠與腦損傷後的排尿效率，從69%降至28%，由尿動力學參數發現，腦損傷鼠在排尿時，膀胱收縮時間以及膀胱收縮壓皆減少，說明腦損傷的大鼠其膀胱處於遲鈍狀態。經由我們自製的回饋式深腦電刺激器的治療，膀胱收縮時間以及膀胱收縮壓皆有改善的效果，排尿效率從腦損傷後的28%提升至70%以上，由此證實了以深腦電刺激模式能對腦損傷鼠的排尿功能改善做出貢獻。
並列摘要
According to FDA statistics in 2012, accident injuries was the top ten causes of death, in which twenty percent of death were resulted from traumatic brain injury. With medical technology development which leads to the significant enhancement of survival rate. But it always leads to the motor, sensation, and urinary system disorders in most of patients in their life span due to the permanent damage of brain tissue. The chronic voiding dysfunction would likely cause urinary tract infections, incontinence, severe and even lead to kidney failure or death. Therefore, the patient with voiding dysfunctions can not be ignored. In clinical treatment, there is no convenience or effective approaches for improving urination. Previous literature shows that patients receiving long-term deep brain stimulation, not only enhance the motor function, but also improve the bladder functions. Therefore, deep brain stimulation could be a new solution for this disease. On the other hand, it is very important to detect the status of a bladder, and to give the deep brain stimulation at the right time. Clinical detection of the bladder status nowadays depends on urodynamic study, such as the volume of the bladder by external ultrasound, or the intravesical pressure by catheterization. However, external ultrasound can not give the electrical neural moderation immediate feedback, and long-term catheterization is also unsuitable for patients. The purpose of this study was to use neural engineering aspect for constructing a stable brain damage animal model and automatic stimulator which feedback signal is to use external urethral sphincter electromyography (EUS-EMG) as detector of the bladder status, then apply the deep brain stimulation at the suitable time in the rats which is suffering from traumatic brain injury. In result, a significant decrease in average cystometrogram (CMG) was detected in rats one week after traumatic brain injury. Abnormal urodynamic measurements including contraction amplitude, residual volume as well as contraction duration were decrease, and indicated inefficient voiding. To treat these symptom, using low frequency (50Hz with 1V to 2.5V) deep brain stimulation of the pontine reticular nucleus (PnO) is a potential method for underactive bladder. After deep brain stimulation, voiding efficiency increased from 28% to 70%. These results raise the possibility that using low frequency deep brain stimulation to excite detrusor contraction which may provide a new approach for improving voiding in traumatic brain injury patients.