正常脊髓內的血管外圍具有特殊的血管障壁，可保護脊髓組織免受血液中發炎細胞與有害物質的傷害。當脊髓受到創傷之後，外力的傷害不僅切斷神經纖維，同時也破壞血管障壁，發炎細胞得以滲入神經組織使傷口惡化。因此，重建受損的血管障壁是傷口復原的關鍵要素，因為健全的血管可以提供豐富的氧氣與養分促進修復。完整的血管障壁應具備三層結構，分別為緊密結合之內皮細胞、基底膜與星狀膠細胞的終足。過去研究顯示脊髓受創後，傷口修復過程中會自發性出現新生的血管，然而血管新生卻無助肢體運動功能的恢復，由此推測新生血管的血管障壁可能有缺損。因此，本論文所研究的問題為：脊髓損傷後自發性新生的血管是否和正常的血管一樣擁有結構完整的血管障壁？本研究運用脊髓胸段中度挫傷手術後的成年小鼠作為實驗組，與未接受手術之對照組作比較，透過西方墨點與免疫組織化學染色實驗得知特定細胞外基質在損傷後的表現量會顯著增加。脊髓受創傷後確實在損傷區域有自發性血管重建，其形態多為扭曲不規則狀。穿透式電子顯微鏡的觀察結果進一步證實這些血管的血管障壁並不完整，缺少基底膜或星狀膠細胞終足之覆蓋。儘管新生血管數量會逐漸增加，但卻與肢體運動功能的恢復沒有顯著關聯。我的研究結果對未來開發脊髓創傷療法提供了一個新的思考方向，除了增加新生血管的密度之外，更應重視重建完整血管障壁的重要性。

The spinal cord parenchyma is protected from harmful substances in the blood by a vascular barrier, which consists of astrocytic processes, extracellular matrix molecules, and endothelial cells. After spinal cord injury, this vascular barrier is disrupted, leading to infiltration of inflammatory cells that further damage the tissue. During wound healing, revascularization occurs spontaneously in the lesion center where there is no astrocyte in injured mouse spinal cord. As such, how astrocytes in the uninjured area extend processes to wrap newly-formed blood vessels in the lesion center is unknown. Moreover, recent studies showed that increasing the vascular density in the lesion does not improve neural regeneration, raising a question whether or not the newly-formed blood vessels possess an intact vascular barrier. Therefore, I proposed to characterize revascularization in the mouse spinal cord subjected to a moderate mid-thoracic contusion injury. I found that the expression of matrix molecules including fibronectin, laminin, and collagen type IV increased after injury. As demonstrated by electron microscopy, moreover, most of the newly-formed blood vessels possessed disintegrated basement membrane, both immature and mature junctional complexes between endothelial cells, and compromised perivascular astrocytes, indicating a defective vascular barrier. Furthermore, increased density of these blood vessels was not associated with the recovery of hindlimb motor function. My results provide the first ultrastructural evidence demonstrating an abnormal vascular barrier of the newly-formed blood vessels in the injured spinal cord. It draws constructive clues for developing therapies to promote wound healing after spinal cord injury.

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