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研究生:杜宗熹
研究生(外文):Tsung-Hsi Tu
論文名稱:酸性纖維母細胞生長素於中樞神經系統損傷治療之角色
論文名稱(外文):Strategies to Repair the Central Nervous System Injury: The role of Acidic Fibroblast Growth Factor
指導教授:鄭宏志鄭宏志引用關係
指導教授(外文):Henrich Cheng
學位類別:博士
校院名稱:國立陽明大學
系所名稱:分子醫學博士學位學程
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2019
畢業學年度:108
語文別:英文
論文頁數:98
中文關鍵詞:脊髓損傷臂神經叢損傷酸性纖維母細胞生長素神經保護
外文關鍵詞:spinal cord injurybrachial plexus injuryacidic fibroblast growth factorneuroprotection
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中樞神經系統損傷是醫學界亟欲突破的治療難題,其對於病人以至於家庭與社會的影響巨大。本研究論文涵蓋兩大主題,靈長類節前臂神經叢損傷模型及齧齒類脊髓損傷實驗,應用酸性纖維母細胞生長酵素(acidic Fibroblast Growth Factor, aFGF)以及天然藥物治療脊髓中樞神經損傷,分別探討:一、使用酸性纖維母細胞生長酵素aFGF,配合顯微手術於治療以台灣獼猴建立之節前型臂神經叢損傷模型,證明靈長類上肢的動作進步與組織學上的神經軸突生長以及神經組織保護,在使用aFGF後均有正面成效。二、應用天然藥物於治療齧齒類衝擊性脊髓損傷模型,揭示齧齒類後肢的功能進步以及組織學的發炎反應減少。

本研究論文顯示包括脊髓損傷及節前臂神經叢損傷等中樞神經系統損傷之嚴重性與長期影響,並證實上揭治療方法是實際可行的中樞神經系統損傷治療策略,驗證合併酸性纖維母細胞生長酵素aFGF及其他策略治療中樞神經損傷之安全性及有效性,未來將延伸此實驗的成果更進一步轉譯到臨床試驗,持續進中樞神經系統損傷之治療研究。
Repair of the injured central nervous system remains a daunting challenge. Such injuries usually have tremendous devastating effects for the patients, their families, and for society. This thesis covers two main aspects for the repair of CNS injuries: a primate preganglionic brachial plexus injury (BPI) model using acidic fibroblast growth factor (aFGF), and the treatment of rodent contusion spinal cord injury with natural products. The proposed treatment strategy for the primate improves functional recovery of the injured primate and also attenuates the damage of the spinal cord caused by the preganglionic root injury. These results prove the benefits of aFGF in the repair of primate preganglionic BPI. The natural products improved hindlimb functions in the rat spinal cord injury.

The severity and long-term effects of CNS injury, such as spinal cord injury and preganglionic cervical root injury, warrant the development of reliable and safe treatment strategies, including application of aFGF and other factors in combination. The results from these studies will be translated into clinical application to further expand the treatment armamentarium of central nervous system injuries.
Table of Contents
Acknowledgement i
Chinese Abstract ii
English Abstract iii
List of Abbreviation iv
Table of Content v
1. Introduction 1
1.1 Preganglionic brachial plexus injury (BPI) 7
1.1.1 Current treatment options of preganglionic BPI 8
1.1.2 Difficulties in the recovery from preganglionic BPI 10
1.2 Natural products in the treatment of spinal cord injury 11
1.2.1 Scutellaria baicalensis Georgi (Sb) and Bupleurum scorzonerifolfium Willd (Bs) (S/B remedy) as an herbal medicine 12
1.2.2 Spinal cord contusion model 13
2. Materials and Method 14
2.1 Study 1 14
2.1.1 Study design and animal model experiment protocol 14
2.1.2 Surgery 16
2.1.3 Behavioral training and evaluation 19
2.1.4 Electrophysiologic study 22
2.1.5 Retrograde axonal tracing 23
2.1.6 Perfusion for neural tissue procurement and analysis 24
2.1.7 Histology and immunohistochemistry 24
2.1.8 Image Quantification 27
2.2 Study 2 28
2.2.1 Reagents and Antibodies 28
2.2.2 Preparation of S/B remedy 28
2.2.3 Animals 29
2.2.4 Neuronal/Glial Cultures 29
2.2.5 Mixed glial cultures and microglial cultures 30
2.2.6 Spinal cord contusion and treatment 31
2.2.7 Biochemical Assays 32
2.2.8 Western blot analysis 33
2.2.9 Histological examination of spinal cord injury 34
3. Results 35
3.1 Study 1 35
3.1.1 Anatomy of brachial plexus in Macaca cyclopis 35
3.1.2 aFGF improved sensory and motor circuit recovery 36
3.1.3 aFGF attenuates astrocytic and microglial activation after cervical preganglionic root injury 39
3.1.4 aFGF decreases demyelination in the spinal cord after cervical preganglionic root injury 42
3.1.5 Behavior evaluation 44
3.1.6 Electrophysiological evaluation 48
3.2 Study 2 49
3.2.1 Anti-inflammatory and anti-oxidative activities of S/B remedy in spinal cord neuronal/glial cultures 49
3.2.2 Anti-inflammatory and anti-oxidative effect of the S/B remedy in microglial cultures 52
3.2.3 Inhibition of microglial activation in the injured spinal cords and improvement of hindlimb functional restoration of SCI rats 55
4. Discussion 62
4.1 Preganglionic brachial plexus injury 62
4.2 Herbal medicine in the treatment of spinal cord injury 69
5. Conclusion 73
6. Perspectives 75
7. References 77
8. Publications 89
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