|
|
||||||||
From the Clinical Investigation Section (Stroke Branch), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
Address correspondence and reprint requests to Dr. Thomas J. DeGraba, The National Institutes of Health, NINDS-Stroke Branch, 36 Convent Dr., MSC 4128, Bldg. 36/4A-03, Bethesda, MD 20892.
Abstract.
A growing body of evidence, primarily from animal models of cerebral ischemia and preliminary human studies, indicates that inflammatory mechanisms contribute to secondary neuronal injury after acute cerebral ischemia. Ischemia followed by reperfusion rapidly leads to the expression of inflammatory cytokines, particularly tumor necrosis factor-
and interleukin-1β, which stimulate a complex cascade of events involving local endothelial cells, neurons, astrocytes, and perivascular cells. A secondary response includes the release of other cytokines, an increase in components of the coagulation system, an upregulation of cell adhesion molecule expression, and changes in the expression of components of the immune response. The net effect of these events is transformation of the local endothelium to a prothrombotic/proinflammatory state and induction of leukocyte migration to the site of injury. A number of studies have shown that leukocyte migration occurs within hours of reperfusion. Leukocytes accumulate in the injured region, where they cause tissue injury by several mechanisms, including occlusion of microvasculature, generation of oxygen free radicals, release of cytotoxic enzymes, alteration of vasomotor reactivity, and increase in cytokine and chemoattractant release. Monoclonal antibodies against leukocyte adhesion molecules have been shown to reduce infarct volume in animal models of ischemia-reperfusion. However, this treatment failed to show benefit in the Enlimomab Acute Stroke Trial. A number of factors may complicate the use of antibody directed adhesion molecule blockade in acute stroke and will be discussed in this article. Overall, an increased understanding of inflammatory and immunologic mechanisms still offers great potential for reducing acute stroke injury.
This article has been cited by other articles:
![]() |
J.-Y. Han, Y. Horie, J.-Y. Fan, K. Sun, J. Guo, S. Miura, and T. Hibi Potential of 3,4-dihydroxy-phenyl lactic acid for ameliorating ischemia-reperfusion-induced microvascular disturbance in rat mesentery Am J Physiol Gastrointest Liver Physiol, January 1, 2009; 296(1): G36 - G44. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. A. Naidu, E. S. Fu, E. T. Sutton, L. D. Prockop, and A. Cantor The Therapeutic Effects of Epidural Intercellular Adhesion Molecule-1 Monoclonal Antibody in a Rabbit Model: Involvement of the Intercellular Adhesion Molecule-1 Pathway in Spinal Cord Ischemia Anesth. Analg., September 1, 2003; 97(3): 857 - 862. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Ishikawa, D. Cooper, J. Russell, J. W. Salter, J. H. Zhang, A. Nanda, and D. N. Granger Molecular Determinants of the Prothrombogenic and Inflammatory Phenotype Assumed by the Postischemic Cerebral Microcirculation Stroke, July 1, 2003; 34(7): 1777 - 1782. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Mocco, T. Choudhri, J. Huang, E. Harfeldt, L. Efros, C. Klingbeil, V. Vexler, W. Hall, Y. Zhang, W. Mack, et al. HuEP5C7 as a Humanized Monoclonal Anti-E/P-Selectin Neurovascular Protective Strategy in a Blinded Placebo-Controlled Trial of Nonhuman Primate Stroke Circ. Res., November 15, 2002; 91(10): 907 - 914. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Ding, J. Li, J. A. Rafols, J. W. Phillis, and F. G. Diaz Prereperfusion Saline Infusion Into Ischemic Territory Reduces Inflammatory Injury After Transient Middle Cerebral Artery Occlusion in Rats Stroke, October 1, 2002; 33(10): 2492 - 2498. [Abstract] [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] |
||||
![]() |
B. Krishnadasan, C. R. Hampton, J. Griscavage-Ennis, R. J. Dabal, and E. D. Verrier Molecular Mechanisms of Neurologic Injury Following Cardiopulmonary Bypass Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 2002; 6(1): 43 - 53. [Abstract] [PDF] |
||||
![]() |
M. Campanella, C. Sciorati, G. Tarozzo, and M. Beltramo Flow Cytometric Analysis of Inflammatory Cells in Ischemic Rat Brain Stroke, February 1, 2002; 33(2): 586 - 592. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Bao, K. Sato, M. Li, Y. Gao, R. Abid, W. Aird, M. Simons, and M. J. Post PR-39 and PR-11 peptides inhibit ischemia-reperfusion injury by blocking proteasome-mediated Ikappa Balpha degradation Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2612 - H2618. [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] |
||||
![]() |
W.-D. Heiss, L. W. Kracht, A. Thiel, M. Grond, and G. Pawlik Penumbral probability thresholds of cortical flumazenil binding and blood flow predicting tissue outcome in patients with cerebral ischaemia Brain, January 1, 2001; 124(1): 20 - 29. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. E. Marik Fever in the ICU Chest, March 1, 2000; 117(3): 855 - 869. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Yrjanheikki, T. Tikka, R. Keinanen, G. Goldsteins, P. H. Chan, and J. Koistinaho A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window PNAS, November 9, 1999; 96(23): 13496 - 13500. [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] |
||||
![]() |
W.-D. Heiss, A. Thiel, M. Grond, and R. Graf Which Targets Are Relevant for Therapy of Acute Ischemic Stroke? Stroke, July 1, 1999; 30(7): 1486 - 1489. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |