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on May 20, 2004

Stroke. 2004
Published online before print May 20, 2004, doi: 10.1161/01.STR.0000130592.71028.92
A more recent version of this article appeared on July 1, 2004
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Submitted on November 24, 2003
Revised on March 9, 2004
Accepted on March 25, 2004

Cerebral Neutrophil Recruitment, Histology, and Outcome in Acute Ischemic Stroke. An Imaging-Based Study

C. J.S. Price MRCP*; D. K. Menon PhD; A. M. Peters MD; J. R. Ballinger PhD; R. W. Barber MSc; K. K. Balan MD; A. Lynch PhD; J. H. Xuereb MD, FRCPath; T. Fryer PhD; J. V. Guadagno MRCP; and E. A. Warburton DM

From the University of Cambridge Department of Medicine (C.J.S.P.) and Anaesthesia Section (D.K.M.), Addenbrookes Hospital, Cambridge, UK; Department of Nuclear Medicine (A.M.P., J.R.B., R.W.B., K.K.B.), and Department of Clinical Neurosciences (E.A.W.), Cambridge University Teaching Hospitals Trust, Cambridge, UK; Centre for Applied Medical Statistics (A.L.), Department of Pathology (J.H.X.), Wolfson Brain Imaging Centre (T.F.), and Department of Neurology (J.V.G.), University of Cambridge, UK.

* To whom correspondence should be addressed. E-mail: cp252{at}medschl.cam.ac.uk.

Background and Purpose--Evidence now exists for a pathogenic role for neutrophils in acute cerebral ischemia. We have studied the patterns and temporal profile of cerebral neutrophil recruitment to areas of acute ischemic stroke (IS) and have attempted to correlate this with neurological status and outcome.

Methods--Patients with cortical middle cerebral artery (MCA) IS were recruited within 24 hours of clinical onset. Neutrophil recruitment was studied using indium-111 (111In) troponolate-labeled neutrophils, planar imaging, and single-photon emission computed tomography (SPECT). Volume of brain infarction was calculated from concurrent computed tomography (CT). Hematoxylin and eosin sections were obtained postmortem (n=2). Outcome was measured using Barthel, Rankin, and National Institute of Health Stroke (NIHSS) scales.

Results--Fifteen patients were studied. Significant 111In-neutrophil recruitment to ipsilateral hemisphere, as measured by asymmetry index (AI), was demonstrated within 24 hours of onset in 9 patients; this response was heterogenous between patients and on repeated measurement attenuated over time. Histologically, recruitment was confirmed within intravascular, intramural, and intraparenchymal compartments. Interindividual heterogeneity in neutrophil response did not correlate with infarct volume or outcome. In an exploratory analysis, neutrophil accumulation appeared to correlate significantly with infarct expansion (Spearman rho=0.66; P=0.03, n=12).

Conclusions--Neutrophils recruit to areas of ischemic brain within 24 hours of symptom onset. This recruitment attenuates over time and is confirmed histologically. While neutrophil accumulation may be associated with either the magnitude or the rate of infarct growth, these results require confirmation in future studies.


Key words: stroke • ischemia • neutrophils • SPECT • histology




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