腦腫瘤為造成腦損傷的主要原因，在腦腫瘤中，神經膠母細胞瘤是最常見的初發腦癌腫瘤，它的預後情況相當不樂觀，是屬於復發率高、死亡率高的癌症之一，腦水腫是由腦腫瘤所引起的併發症而病人有可能因為腦水腫造成死亡，這也是為什麼我們要探討由腫瘤所引發腦水腫的原因。腫瘤周圍常伴隨著慢性發炎反應，發炎反應會使細胞釋放出各式各樣的細胞激素，因此，我的實驗主要是探討對於神經膠母細胞瘤所導致的腦水腫中，細胞激素的釋出及變化對細胞、血管通透性、腦組織的影響。
免疫組織染色法實驗結果顯示，免疫細胞中的T細胞、B細胞和巨噬細胞的浸潤有增加；腫瘤壞死因子α (tumoro necrosis factor-α, TNF-α)、腫瘤壞死因子受器1 (tumoro necrosis factor receptor, TNFR1)、介白素1β (Interleukin-1 β, )、干擾素γ (Interferon γ, IFN-γ) 、誘導型一氧化氮合酶 (iNOS)、內皮型一氧化氮合酶 (eNOS) 和嘌呤受體 (P2X7R) 在打入神經膠母細胞瘤細胞株(CNS-1) 而產生腦水腫的實驗組別中，這些細胞激素及受器表現量也有上升的情形。而西方式點墨法也驗證了，打入腫瘤22天後會產生較多的腫瘤壞死因子α，這些結果顯示發炎反應及細胞激素發生於腫瘤所導致的腦水腫模型；免疫組織染色法中，用來標記活化的小神經膠細胞的蛋白質有OX-6、OX42和ED-1，經由觀察在打入腫瘤22天後確實有活化的小神經膠細胞，在西方式點墨法中，證明了在打入腫瘤細胞株22天的組別，小神經膠細胞OX-6有明顯的活化；在腫瘤壞死因子α和小神經膠細胞的雙重螢光染色實驗顯示，活化的小神經膠細胞會釋出TNF-α並隨著時間有漸漸上升；藉由腫瘤壞死因子受器1、嘌呤受體P2X7R、誘導型一氧化氮合酶和內皮型一氧化氮合酶與星狀神經膠細胞的雙重螢光染色實驗顯示在打入腫瘤細胞株後星狀神經膠細胞上都有腫瘤壞死因子受器1和嘌呤受體P2X7R的表現及一氧化氮的釋出都有上升的情形
根據這些實驗結果我們可以下一個結論：腫瘤所引起的腦水腫，確實會使細胞激素、細胞激素受器和一氧化氮合酶的表現量改變，上升的腫瘤壞死因子α、介白素1β 、干擾素γ和一氧化氮會使血管通透性增加和造成血腦障壁的瓦解，使得全身的細胞可通過血腦障壁並且釋放出更多的細胞激素與一氧化氮，這些實驗結果將可以更了解細胞毒性及血管性這兩種腦水腫類型的形成並提供病理生理學重要的資訊用於探討惡性神經膠母細胞瘤旁水腫生成的原因。

Glioblastoma (GBM) is the most common and malignant type of primary brain tumor that carries a poor prognosis, high recurrent rate and mortality. GBM causes direct injury to the brain tissue. Brain edema, one of complications caused by GBM, may result in death of patient. That is why we want to study and discuss tumor-induced brain edema. Focal chronic inflammation, adjacent to the site of tumor growth, may attract and recruit infiltrating of diverse cellular populations which are capable of producing array of cytokines. To characterize the role of cytokines in brain edema, Sprague-Dawley (SD) rats injected with CNS-1 GBM cell line were used to establish a glioma-induced brain edema model. Results of Immunohistochemical (IHC) staining showed that T-cell (CD3), B-cell (CD20) and macrophage (CD68) were focally increased in the tumor. IHC staining results also showed that expression of tumor necrosis factor-α (TNF-α), tumor necrosis factor receptor (TNFR1), interleukin-1β (IL-1β), interferon-γ (IFN-γ), inducible nitric oxide synthases (iNOS), endothelia nitric oxide synthases (eNOS) and P2X7 receptors (P2X7Rs) were gradually increased with our time-course study in CNS-1-injected groups. Western blotting (WB) results showed dramatically increased TNF-α in 22 day-post CNS-1-injected group, which suggests inflammation and cytokines release follow growth of tumor and severity of inflammation in tumor-induced brain edema. By using microglial markers OX-6, OX42 and ED-1, activated microglia was detected on 22 day-post CNS-1-injected group, which is further supported by WB results on OX-6 blotted brain protein homogenate. Double immunofluorescence (IF) staining was used to verify TNF-α. was released by microglia. Double IF staining of astrocyte marker GFAP with TNFR1, P2X7Rs, iNOS, and eNOS showed that the receptors were expressed in reactive astrocytes and astrocytes also produced nitric oxide (NO).
According to these results, our model showed the changed expression of cytokines, cytokine’s receptor and NO. The increases of TNF-α, IL-1β, IFN-γ and NO which are associated with increased vascular permeability and blood-brain barrier (BBB) disruption which may make systematic cells pass through BBB and released more cytokines and NO. Taken together, these results may be related to cytotoxic and vasogenic component and provide useful information to study detail pathophysiological mechanisms in the genesis of tumor-induced brain edema.

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