title: Inflammation in stroke and focal cerebral ischemia.
abstract: BACKGROUND
  A growing number of recent investigations have established a critical role for leukocytes in propagating tissue damage after ischemia and reperfusion in stroke. Experimental data obtained from animal models of middle cerebral artery occlusion implicate inflammatory cell adhesion molecules, chemokines, and cytokines in the pathogenesis of this ischemic damage.
  
  
  METHODS
  Data from recent animal and human studies were reviewed to demonstrate that inflammatory events occurring at the blood-endothelium interface of the cerebral capillaries underlie the resultant ischemic tissue damage.
  
  
  RESULTS
  After arterial occlusion, the up-regulated expression of cytokines including IL-1, and IL-6 act upon the vascular endothelium to increase the expression of intercellular adhesion molecule-1, P-selectin, and E-selectin, which promote leukocyte adherence and accumulation. Integrins then serve to structurally modify the basal lamina and extracellular matrix. These inflammatory signals then promote leukocyte transmigration across the endothelium and mediate inflammatory cascades leading to further cerebral infarction.
  
  
  CONCLUSIONS
  Inflammatory interactions that occur at the blood-endothelium interface, involving cytokines, adhesion molecules, chemokines and leukocytes, are critical to the pathogenesis of tissue damage in cerebral infarction. Exploring these pathophysiological mechanisms underlying ischemic tissue damage may direct rational drug design in the therapeutic treatment of stroke.
authors.affiliation: Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Judy
authors.initials: J
authors.lastname: Huang
authors.forename: Urvashi M
authors.initials: UM
authors.lastname: Upadhyay
authors.forename: Rafael J
authors.initials: RJ
authors.lastname: Tamargo
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology / Q000503:physiopathology*; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D002545:Brain Ischemia / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004660:Encephalitis / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000276:immunology; D006801:Humans; D015398:Signal Transduction / Q000276:immunology; D020521:Stroke / Q000150:complications / Q000276:immunology / Q000503:physiopathology*
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines