Basic research for the comprehensive analysis of selective whitematter injury and the axonal regeneration

使用Sprague-Dawley大鼠。在全麻下向一侧内囊立体定向注射内皮素-1（ET-1：0.5μg/μl）诱导选择性白色损害，MRI检查选择性白色损害，特别是轴索损伤，应用APP免疫反应证实。注射后3天至2周，ED 1免疫反应增强，显示活化的小胶质细胞迁移并占据白色损伤灶。质谱成像技术（Imaging mass spectrometry，IMS）能全面地揭示磷脂酰胆碱的动态变化，为揭示传统成像技术所不能揭示的分子动态变化提供了新的思路。将MVECs移植于内囊缺血区。MVEC移植改善了行为学结果并诱导了髓鞘再生。MVEC移植还抑制了炎症反应。阐明MVEC改善白色物质缺血性损伤的机制可能为白色物质缺血的有效治疗提供重要信息。

Sprague-Dawley rats were used. Under general anesthesia endothelin-1(ET-1:0.5μg/μl) was stereotactically injected into unilateral internal capsule to induce selective white matter damage.Selective white matter injury was evaluated by MRI, and particularly axonal injury was confirmed by specific APP immunoreactivity. The increased immunoreactivitiy for ED1 was observed in the lesion from3 days to 2 weeks after injection showing the activated microglia migrated and occupied the lesion of white matter injury. Imaging mass spectrometry (IMS) revealed the dynamicchange of phosphatidylcholines comprehensively IMS has tremendous potentials to provide the new insight in terms of the dynamic molecular changes invisible under conventional modality.The microvascular endothelial cells (MVECs) were prepared from rat cerebra for the cell transplantation. MVECs were transplanted into the ischemic lesion of internal capsule. MVECtransplantation improved the behavioral outcome and induced remyelion. Also the inflammatory response was repressed by MVEC transplantation. Elucidation of the mechanisms by which MVECs ameliorate ischemic damage of the white matter mayprovide important information for the development of effective therapies for white matter ischemia.