(Circulation. 1996;94:939-945.)
© 1996 American Heart Association, Inc.
Articles |
Endothelial ICAM-1 Expression Associated With Inflammatory Cell Response in Human Ischemic Stroke
the Department of Neurology (P.J.L., M.K.) and the Department of Pathology (O.C., A.P., M.-L.K.-L.), University of Helsinki (Finland).
Correspondence to Dr P.J. Lindsberg, Department of Neurology, University of Helsinki, Haartmaninkatu 4, FIN-00290 Helsinki, Finland.
Background After focal brain ischemia, leukocytes adhere to the perturbed endothelium and are believed to aggravate reperfusion injury. Although ischemia-induced upregulation of endothelial adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and P-selectin, has been observed in experimental animals, the mechanism of cerebral leukocyte infiltration and thus therapeutic possibilities to reduce it in humans are uncertain.
Methods and Results We counted the granulocytes, mononuclear phagocytes, and the percentages of cerebral microvessels expressing ICAM-1 by applying immunohistochemistry on brain sections showing a variable degree of neuronal damage from 11 human subjects who died 15 hours to 18 days after ischemic stroke and from normal control brains. In infarcted regions, granulocytes were detected as early as at 15 hours after injury (11.3 versus 0.5 cells/mm2 in noninfarcted hemisphere); their amount exceeded 200 cells/mm2 by 2.2 days but was back to normal level at 6.3 and 8.5 days. Acute infarctions (0.6 to 8.5 days) harbored significantly more ICAM-1–stained microvessels (up to 97% of microvessels at 1.8 days) than the noninfarcted hemisphere (P<.001), although the noninfarcted hemisphere (1.8 to 6.3 days) also showed higher ICAM-1 expression than controls. In the absence of ICAM-1 upregulation, macrophages (>200/mm2) were abundant in the core of neuronal damage at 17 and 18 days.
Conclusions The striking upregulation of endothelial ICAM-1 expression, functioning in concert with chemotactic factors, may cause granulocyte infiltration during the first 3 days after stroke. This study may support the usage and timing of antibody infusions to block endothelial adhesion molecules in an attempt to reduce leukocyte-induced damage in stroke.
Key Words: molecular biology • leukocytes • microcirculation • stroke
This article has been cited by other articles:
 |
|
 |
|
  A. Kunz, T. Abe, K. Hochrainer, M. Shimamura, J. Anrather, G. Racchumi, P. Zhou, and C. Iadecola Nuclear Factor-{kappa}B Activation and Postischemic Inflammation Are Suppressed in CD36-Null Mice after Middle Cerebral Artery Occlusion J. Neurosci., February 13, 2008; 28(7): 1649 - 1658. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Strbian, M.-L. Karjalainen-Lindsberg, P. T. Kovanen, T. Tatlisumak, and P. J. Lindsberg Mast Cell Stabilization Reduces Hemorrhage Formation and Mortality After Administration of Thrombolytics in Experimental Ischemic Stroke Circulation, July 24, 2007; 116(4): 411 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Nighoghossian, M. Wiart, S. Cakmak, Y. Berthezene, L. Derex, T.-H. Cho, C. Nemoz, F. Chapuis, G.-L. Tisserand, J.-B. Pialat, et al. Inflammatory Response After Ischemic Stroke: A USPIO-Enhanced MRI Study in Patients Stroke, February 1, 2007; 38(2): 303 - 307. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sairanen, M.-L. Karjalainen-Lindsberg, A. Paetau, P. Ijas, and P. J. Lindsberg Apoptosis dominant in the periinfarct area of human ischaemic stroke--a possible target of antiapoptotic treatments Brain, January 1, 2006; 129(1): 189 - 199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Coats and R. Wadsworth Marriage of resistance and conduit arteries breeds critical limb ischemia Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1044 - H1050. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.J. S. Price, D.K. Menon, A.M. Peters, J.R. Ballinger, R.W. Barber, K.K. Balan, A. Lynch, J.H. Xuereb, T. Fryer, J.V. Guadagno, et al. Cerebral Neutrophil Recruitment, Histology, and Outcome in Acute Ischemic Stroke: An Imaging-Based Study Stroke, July 1, 2004; 35(7): 1659 - 1664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hassan, B. J. Hunt, M. O'Sullivan, R. Bell, R. D'Souza, S. Jeffery, J. M. Bamford, and H. S. Markus Homocysteine is a risk factor for cerebral small vessel disease, acting via endothelial dysfunction Brain, January 1, 2004; 127(1): 212 - 219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C J S Price, E A Warburton, and D K Menon Human cellular inflammation in the pathology of acute cerebral ischaemia J. Neurol. Neurosurg. Psychiatry, November 1, 2003; 74(11): 1476 - 1484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Taipale, N. Kaminen, J. Nopola-Hemmi, T. Haltia, B. Myllyluoma, H. Lyytinen, K. Muller, M. Kaaranen, P. J. Lindsberg, K. Hannula-Jouppi, et al. From the Cover: A candidate gene for developmental dyslexia encodes a nuclear tetratricopeptide repeat domain protein dynamically regulated in brain PNAS, September 30, 2003; 100(20): 11553 - 11558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Lees, H.-C. Diener, K. Asplund, and M. Krams UK-279,276, a Neutrophil Inhibitory Glycoprotein, in Acute Stroke: Tolerability and Pharmacokinetics Stroke, July 1, 2003; 34(7): 1704 - 1709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Nuotio, P. J. Lindsberg, O. Carpen, L. Soinne, E. M.P. Lehtonen-Smeds, E. Saimanen, R. Lassila, T. Sairanen, S. Sarna, O. Salonen, et al. Adhesion molecule expression in symptomatic and asymptomatic carotid stenosis Neurology, June 24, 2003; 60(12): 1890 - 1899. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hassan, B. J. Hunt, M. O'Sullivan, K. Parmar, J. M. Bamford, D. Briley, M. M. Brown, D. J. Thomas, and H. S. Markus Markers of endothelial dysfunction in lacunar infarction and ischaemic leukoaraiosis Brain, February 1, 2003; 126(2): 424 - 432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F-E. de LEEUW, M. de KLEINE, C. J. M. FRIJNS, R. FIJNHEER, J. van GIJN, and L. J. KAPPELLE Endothelial Cell Activation Is Associated with Cerebral White Matter Lesions in Patients with Cerebrovascular Disease Ann. N.Y. Acad. Sci., November 1, 2002; 977(1): 306 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J Kraus, P Oschmann, S Leis, B Neundorfer, and J G Heckmann High concentrations of sVCAM-1 and sICAM-1 in the cerebrospinal fluid of patients with intracerebral haemorrhage are associated with poor outcome J. Neurol. Neurosurg. Psychiatry, September 1, 2002; 73(3): 346 - 347. [Full Text] [PDF]
|
|
|
|
|
|
C.J.M. Frijns and L.J. Kappelle Inflammatory Cell Adhesion Molecules in Ischemic Cerebrovascular Disease Stroke, August 1, 2002; 33(8): 2115 - 2122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. THOMAS, I. N. FERRIER, R. N. KALARIA, S. DAVIS, and J. T. O'BRIEN Cell adhesion molecule expression in the dorsolateral prefrontal cortex and anterior cingulate cortex in major depression in the elderly The British Journal of Psychiatry, August 1, 2002; 181(2): 129 - 134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Use of anti-ICAM-1 therapy in ischemic stroke: Results of the Enlimomab Acute Stroke Trial Neurology, October 23, 2001; 57(8): 1428 - 1434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J J Nissen, D Mantle, B Gregson, and A D Mendelow Serum concentration of adhesion molecules in patients with delayed ischaemic neurological deficit after aneurysmal subarachnoid haemorrhage: the immunoglobulin and selectin superfamilies J. Neurol. Neurosurg. Psychiatry, September 1, 2001; 71(3): 329 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sairanen, O. Carpen, M.-L. Karjalainen-Lindsberg, A. Paetau, U. Turpeinen, M. Kaste, P. J. Lindsberg, and D. F. Cechetto Evolution of Cerebral Tumor Necrosis Factor-{alpha} Production During Human Ischemic Stroke Editorial Comment Stroke, August 1, 2001; 32(8): 1750 - 1758. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Caimi, F. Ferrara, M. Montana, F. Meli, B. Canino, C. Carollo, and R. L. Presti Acute Ischemic Stroke : Polymorphonuclear Leukocyte Membrane Fluidity and Cytosolic Ca2+ Concentration at Baseline and After Chemotactic Activation Stroke, July 1, 2000; 31(7): 1578 - 1582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Lipton Ischemic Cell Death in Brain Neurons Physiol Rev, October 1, 1999; 79(4): 1431 - 1568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Davis and D. Barer Neuroprotection in acute ischaemic stroke. II: Clinical potential Vascular Medicine, August 1, 1999; 4(3): 149 - 163. [Abstract] [PDF]
|
|
|
|
 |
|
 S. I. Savitz and D. M. Rosenbaum Review : Gene Expression after Cerebral Ischemia Neuroscientist, July 1, 1999; 5(4): 238 - 253. [Abstract] [PDF]
|
|
|
|
 |
|
 J. Vuorte, P. J. Lindsberg, M. Kaste, S. Meri, S.-E. Jansson, R. Rothlein, and H. Repo Anti-ICAM-1 Monoclonal Antibody R6.5 (Enlimomab) Promotes Activation of Neutrophils in Whole Blood J. Immunol., February 15, 1999; 162(4): 2353 - 2357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Tarkowski, L. Rosengren, C. Blomstrand, C. Jensen, S. Ekholm, and A. Tarkowski Intrathecal Expression of Proteins Regulating Apoptosis in Acute Stroke Stroke, February 1, 1999; 30(2): 321 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bitsch, W. Klene, L. Murtada, H. Prange, and P. Rieckmann A Longitudinal Prospective Study of Soluble Adhesion Molecules in Acute Stroke Stroke, October 1, 1998; 29(10): 2129 - 2135. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Gidday, T.S. Park, A. R. Shah, E. R. Gonzales, P. M. Kochanek, R. S.B. Clark, and M. J. Whalen Modulation of Basal and Postischemic Leukocyte-Endothelial Adherence by Nitric Oxide • Editorial Comment Stroke, July 1, 1998; 29(7): 1423 - 1430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.J.M. Frijns, L.J. Kappelle, J. v. Gijn, H.K. Nieuwenhuis, J.J. Sixma, and R. Fijnheer Soluble Adhesion Molecules Reflect Endothelial Cell Activation in Ischemic Stroke and in Carotid Atherosclerosis Stroke, November 1, 1997; 28(11): 2214 - 2218. [Abstract] [Full Text]
|
|
|
|
|
|
K.-z. Zhang, P. J. Lindsberg, T. Tatlisumak, M. Kaste, H. S. Olsen, and L. C. Andersson Stanniocalcin: A molecular guard of neurons during cerebral ischemia PNAS, March 28, 2000; 97(7): 3637 - 3642. [Abstract] [Full Text] [PDF]
|
|