臺灣博碩士論文加值系統

神經新生是新生神經元的過程，主要發生在subventricular zone (SVZ)和dentate gyrus (DG)中的 subgranular zone (SGZ)。多種生理狀態及體內物質均可調節神經新生的作用，包括糖皮質素、雌激素、生長因子、神經傳導物質、學習和壓力等。證據顯示某些病理狀態也能刺激神經新生，如癲癇、腦缺氧、頭部外傷和蜘蛛網膜下腔出血(subarachnoid hemorrhage, SAH)。蜘蛛網膜下腔出血多由腦中動脈瘤破裂所導致，具有高死亡率和高發病率，其死亡原因認為與腦部血管痙攣有關。血管內皮生長因子(vascular endothelial growth factor, VEGF)能夠刺激神經先趨細胞和促使神經新生。在我們先前的研究中已顯示，頭部外傷時需具有血管內皮生長因子以誘導神經新生，所以本篇研究旨在評估蜘蛛網膜下腔出血後，血管內皮生長因子對神經新生的影響。我們使用大鼠的雙重出血模式，藉由分別兩次將大鼠自體血液注入至延髓池(cisterna magna)中以誘導蜘蛛網膜下腔出血，並在誘導後以腹腔注射5’-bromo-2’-deoxyuridine (BrdU)以標定新生的細胞。分別以反轉錄-聚合&;#37238;連鎖反應和西方點墨法，偵測血管內皮生長因子mRNA與蛋白質的表現量，另外使用雙重免疫螢光染色法評估BrdU和雙皮質激素(doublecortin, DCX)的數量和分佈。在本篇研究中，我們發現在大腦皮質和海馬迴中，血管內皮生長因子的mRNA和蛋白質表現量皆在蜘蛛網膜下腔出血的七天後有顯著的上升；此外也發現海馬迴中神經新生的現象在蜘蛛網膜下腔出血後的三天內明顯減少，而在第九天時回復到基準值。在投予VEGF antisense oligonucleotides 後使得蜘蛛網膜下腔出血後的神經新生現象顯著的降低。本研究結果顯示血管內皮生長因子在蜘蛛網膜下腔出血後的神經新生中扮演著不可或缺的角色。

Neurogenesis, the process of newly generated neurons, occurs mainly in the subventricular zone (SVZ) and the subgranular zone (SGZ) of the dentate gyrus (DG). Various physiological stimuli could modulate neurogenesis in these regions which include glucocorticoid, estrogen, growth factors, excitatory neurotransmission, learning and stress can be manipulated pharmacologically. It is also evidenced that pathological events can stimulate adult neurogenesis such as seizures, ischemia, traumatic brain injury and subarachnoid hemorrhage (SAH). SAH is a life-threatening disorder of the central nervous system with high mortality and morbidity rates mainly associated with primary brain damage and cerebral vasospasm. Previous results showed vascular endothelial growth factor (VEGF) could stimulate neuronal precursors and promotes neurogenesis. Our previous study demonstrated that VEGF is necessary for traumatic brain injury-induced neurogenesis. The present study aimed to evaluate the effect of VEGF on neurogenesis after SAH. We used double hemorrhage model of SAH by injection of autologous blood twice into cisterna magna of rats. Rats received intraperitoneal injections of 5’-bromo-2’-deoxyuridine (BrdU) after SAH induction. The expression of VEGF was detected by RT-PCR and Western blot. Immunofluorescence double labeling was used to evaluate the distribution of BrdU, doublecortin (DCX) and VEGF. In this study, we found that expression of VEGF mRNA and protein significantly increased in cortex and hippocampus seven days after SAH. We also found that the hippocampal neurogenesis was decreased at day 3 after SAH, and was backed to the normal level at day 9. Administration of VEGF antisense oligonucleotides significantly attenuated SAH-induced neurogenesis. Our study demonstrated that VEGF plays an essential role in hippocampal neurogenesis after SAH.

中文摘要 i
英文摘要 iii
常用縮寫表 v
目錄 vii
圖目錄 viii
第一章 緒論 1
第二章 實驗材料及方法 14
第三章 結果 27
第四章 討論 32
參考文獻 41
圖表 59
附錄 77

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