Hemin induces heme oxygenase-1 in spinal cord vasculature and attenuates barrier disruption and neutrophil infiltration in the injured murine spinal cord

Toshihiro Yamauchi, Yong Lin, Frank R Sharp, Linda J. Noble-Haeusslein

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Heme oxygenase-1 (HO-1) has been shown to alter vascular function in part by attenuating inflammation. We induced HO-1 in blood vessels in the spinal cord by systemic administration of hemin. Twenty-four hours later, immediately prior to euthanasia, fluorescence conjugated Lycopersicon esculentum (tomato) lectin was given intravenously to label the vasculature. HO-1 was induced in blood vessels, particularly in the white matter, as evidenced by the immunolocalization of HO-1 in lectin positive vessels. Western blots confirmed the hemin-mediated induction of HO-1 in the uninjured spinal cord. We next examined the extent to which treatment with hemin or vehicle, 24 h prior to a moderate contusion injury, influenced early vascular dysfunction in the injured cord. All animals were euthanized 24 h after injury. Luciferase, a marker of barrier integrity, was given intravenously 30 min prior to euthanasia. The spinal cord was either prepared for quantification of luciferase activity or fixed by vascular perfusion and prepared for the immunolocalization of neutrophils. There was a significant attenuation of barrier permeability to luciferase and a significant reduction in the number of neutrophils in hemin treated animals as compared to the vehicle treated group. Together, these findings demonstrate that vascular induction of HO-1 modulates barrier function and neutrophil inflitration and suggest that this protein may be useful for limiting the early vascular dysfunction and inflammation that occurs in the acutely injured spinal cord.

Original languageEnglish (US)
Pages (from-to)1017-1030
Number of pages14
JournalJournal of Neurotrauma
Volume21
Issue number8
DOIs
StatePublished - Aug 2004
Externally publishedYes

Keywords

  • Blood-brain barrier
  • Heme oxygenase
  • Inflammation
  • Spinal cord injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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