Cited by 289Spinal Cord Injury ResearchBarrier Structure and Function StudiesTraumatic Brain Injury and Neurovascular Disturbances

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

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Whetstone, William D., Hsu, Jung‐Yu C., Eisenberg, Manuel, Werb, Zena, Noble‐Haeusslein, Linda J.·2003·Journal of Neuroscience Research

Abstract

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.

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  • Some reports suggest that spinal cord injury generates a biphasic opening of the barrier: the first peak of abnormal leakage occurs within several hours after injury, whereas the second peak is evident between 3 and 7 days post-injury.

    “Some reports suggest that SCI generates a biphasic opening of the barrier. The first peak of abnormal leakage occurs within several hours after injury, whereas the second peak is evident between 3 and 7 days post-injury (644).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [644]

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Research works printed but not linked: 3

  1. Cancilla PA, Berliner J. Brain endothelial-astrocyte interactions. New York: Raven Press; 1993. [Google Scholar]
  2. Hayashi Y, Nomura M, Yamagishi S, Harada S, Yamashita J, Yamamoto H. Induction of various blood-brain barrier properties in non-neural endothelial cells by close apposition to co-cultured astrocytes. Glia. 1997;19:13–26. [PubMed] [Google Scholar]
  3. Pardridge WM. Molecular cloning and regulation of gene expression of blood-brain barrier glucose transporter. New York: Raven Press; 1993. [Google Scholar]

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Authors
Whetstone, W. D., Hsu, J. C., Eisenberg, M., Werb, Z., & Noble‐Haeusslein, L. J.
Affiliations
University of California, San Francisco (US)
Corresponding author
Noble‐Haeusslein, Linda J.
Venue
Journal of Neuroscience Research
Publisher
Wiley
Published
2003-08-25
Volume
74
Issue
2
Pages
227-239
ISSN
  • 0360-4012 (ISSN-L)
  • 1097-4547
OpenAlex
W2141244009
Cited by
288
References
42
Citations by year
2026: 14 · 2025: 11 · 2024: 19 · 2023: 23 · 2022: 19 · 2021: 16 · 2020: 17 · 2019: 10 · 2018: 19 · 2017: 9 · 2016: 18 · 2015: 11 · 2014: 13 · 2013: 11 · 2012: 7
FWCI
2.85
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Neurological Disorders and Stroke (NS 39847, NS39278, R01NS039847, R01NS039278)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords
blood-spinal cord barrier, spinal cord injury, revascularization, wound healing, vascular permeability, glucose transporter 1, astrocytes, macrophages, vascular regeneration
MeSH terms
Animals, Astrocytes, Blood Vessels, Blood-Brain Barrier, Gliosis, Luciferases, Macrophages, Male, Mice, Inbred C57BL, Spinal Cord, Spinal Cord Injuries, Wound Healing, Glutamic Acid, Neovascularization, Physiologic, Excitatory Amino Acid Transporter 2, Mice

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