Postischemic cerebrovascular E-selectin expression mediates tissue injury in murine stroke

Judy Huang, Tanvir F. Choudhri, Christopher J. Winfree, Ryan A. McTaggart, Szilard Kiss, J. Mocco, Louis J. Kim, Themistocles S. Protopsaltis, Yuan Zhang, David J. Pinsky, E. Sander Connolly

Research output: Contribution to journalArticle

Abstract

Background and Purpose - Although the deleterious role of several proinflammatory mediators, including P-selectin, in reperfused stroke is well established, the role of E-selectin has not been fully characterized. Methods - E-selectin mRNA expression was studied at 4, 10, and 24 hours after reperfusion with reverse transcription and polymerase chain reaction in mice (n=18) subjected to transient intraluminal middle cerebral artery occlusion (MCAO). Mice received intravenous injection with anti-E-selectin monoclonal antibody (10, 35, or 50 μg), nonimmune IgG, or vehicle immediately before MCAO and 90 minutes later (n=85). Others received anti-E-selectin antibody 3 or 6 hours after MCAO (n=32). Myeloperoxidase activity was measured in sham-operated mice and after 10 hours of reperfusion in saline-, nonimmune IgG-, or anti-E-selectin IgG-treated cohorts (n=17). Serial cerebral blood flow was measured with laser-Doppler flowmetry, and outcomes were assessed by neurological deficits and infarct volumes with the use of planimetric analysis of triphenyltetrazolium chloride-stained sections. Results - Upregulated E-selectin expression occurred in the ischemic cerebral vasculature within 4 hours of reperfusion and persisted for 24 hours. Anti-E-selectin antibody increased ischemic cortical cerebral blood flow up to 2.6-fold (P<0.05). In addition to dose-dependent reductions in neurological deficits (P<0.05), mortality, and infarct volumes (P<0.01 for 35 and 50 μg), anti-E-selectin treatment reduced cerebral neutrophil accumulation (P<0.05) and was neuroprotective even if delayed until 3 hours after ischemia (P<0.05). Conclusions - These findings establish a functional role for E-selectin in the pathogenesis of tissue injury after cerebral ischemia and reperfusion and suggest that E-selectin blockade may be clinically useful in the treatment of reperfused stroke.

Original languageEnglish (US)
Pages (from-to)3047-3053
Number of pages7
JournalStroke
Volume31
Issue number12
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Keywords

  • Cerebral ischemia, focal
  • Cerebral ischemia, transient
  • E-selectin
  • Gene expression
  • Mice

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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  • Cite this

    Huang, J., Choudhri, T. F., Winfree, C. J., McTaggart, R. A., Kiss, S., Mocco, J., Kim, L. J., Protopsaltis, T. S., Zhang, Y., Pinsky, D. J., & Connolly, E. S. (2000). Postischemic cerebrovascular E-selectin expression mediates tissue injury in murine stroke. Stroke, 31(12), 3047-3053. https://doi.org/10.1161/01.STR.31.12.3047