Blood-spinal cord barrier after spinal cord injury: Relation to revascularization and wound healing

• Published in: Journal of neuroscience research Vol. 74; no. 2; pp. 227 - 239
• Main Authors: Whetstone, William D., Hsu, Jung-Yu C., Eisenberg, Manuel, Werb, Zena, Noble-Haeusslein, Linda J.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15-10-2003
• Subjects: Animals; astrocyte; Astrocytes - metabolism; Blood Vessels - cytology; Blood Vessels - growth & development; Blood-Brain Barrier - physiology; Excitatory Amino Acid Transporter 2 - metabolism; Gliosis - physiopathology; glucose-1 transporter; Glutamic Acid - metabolism; luciferase; Luciferases - metabolism; Macrophages - cytology; Macrophages - physiology; Male; Mice; Mice, Inbred C57BL; Neovascularization, Physiologic - physiology; Spinal Cord - blood supply; Spinal Cord - pathology; Spinal Cord - physiopathology; spinal cord contusion injury; Spinal Cord Injuries - pathology; Spinal Cord Injuries - physiopathology; Wound Healing - physiology
• ISSN: 0360-4012; 1097-4547
• 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. © 2003 Wiley‐Liss, Inc.