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

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. E-selectin mRNA expression was studied at 4, 10, and 24 hours after reperfusion with reverse transcription and...

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Published in:	Stroke (1970) 2000-12, Vol.31 (12), p.3047-3053
Main Authors:	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, Jr, E S
Format:	Article
Language:	eng
Subjects:	Animals Brain Ischemia - metabolism Brain Ischemia - physiopathology Cerebrovascular Circulation - physiology Disease Models, Animal E-Selectin - metabolism E-Selectin - physiology Gene Expression Humans Mice Mice, Inbred C57BL Regional Blood Flow - physiology Reperfusion Injury - metabolism Reperfusion Injury - physiopathology Stroke - pathology Stroke - physiopathology Up-Regulation
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Summary:	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. 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 microg), 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. 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:
ISSN:	0039-2499 1524-4628