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.
- Cerebral ischemia, focal
- Cerebral ischemia, transient
- Gene expression
ASJC Scopus subject areas
- Clinical Neurology
- Cardiology and Cardiovascular Medicine
- Advanced and Specialized Nursing