Whetstone William D, Hsu Jung-Yu C, Eisenberg Manuel, Werb Zena, Noble-Haeusslein Linda J
Division of Emergency Medicine, Department of Medicine, University of California, San Francisco, USA.
J Neurosci Res. 2003 Oct 15;74(2):227-39. doi: 10.1002/jnr.10759.
Spinal cord injury produces prominent disruption of the blood-spinal cord barrier. We have defined the blood-spinal cord barrier breakdown to the protein luciferase (61 kDa) in the acutely injured murine spinal cord and during revascularization. We show that newly formed and regenerating blood vessels that have abnormal permeability exhibit differential expression of the glucose-1 transporter (Glut-1), and that its expression is dependent on astrocytes. There was overt extravasation of luciferase within the first hour after injury, a period that coincided with marked tissue disruption within the epicenter of the lesion. Although there was a significant reduction in the number of blood vessels relative to controls by 24 hr after injury, abnormal barrier permeability remained significantly elevated. A second peak of abnormal barrier permeability at 3-7 days postinjury coincided with prominent revascularization of the epicenter. The barrier to luciferase was restored by 21 days postinjury and vascularity was similar to that of controls. During wound-healing process, the cord was reorganized into distinct domains. Between 14 and 21 days postinjury, each domain consisted primarily of nonneuronal cells, including macrophages. Astrocytes were limited characteristically to the perimeter of each domain. Only blood vessels affiliated closely with astrocytes in the perimeter expressed Glut-1, whereas blood vessels within each domain of the repairing cord did not express it. Together, these data demonstrate that both injured and regenerating vessels exhibit abnormal permeability and suggest that Glut-1 expression during revascularization is dependent on the presence of astrocytes.
脊髓损伤会导致血脊髓屏障显著破坏。我们已确定在急性损伤的小鼠脊髓以及血管再生过程中，血脊髓屏障对蛋白质荧光素酶（61 kDa）的屏障功能丧失。我们发现，新形成的和正在再生的血管具有异常通透性，其葡萄糖转运蛋白1（Glut-1）表达存在差异，且该表达依赖于星形胶质细胞。损伤后第一小时内就有明显的荧光素酶外渗，这一时期与损伤中心的明显组织破坏同时发生。尽管损伤后24小时相对于对照组血管数量显著减少，但异常的屏障通透性仍显著升高。损伤后3 - 7天出现的异常屏障通透性第二个峰值与损伤中心的显著血管再生同时发生。损伤后21天时荧光素酶的屏障功能恢复，血管分布与对照组相似。在伤口愈合过程中，脊髓被重新组织成不同的区域。损伤后14至21天，每个区域主要由非神经元细胞组成，包括巨噬细胞。星形胶质细胞典型地局限于每个区域的周边。只有周边与星形胶质细胞紧密相连的血管表达Glut-1，而修复脊髓每个区域内的血管不表达。总之，这些数据表明，损伤的血管和再生的血管均表现出异常通透性，并提示血管再生过程中Glut-1的表达依赖于星形胶质细胞的存在。
