title: Reperfusion injury after focal cerebral ischemia: the role of inflammation and the therapeutic horizon.
abstract: Recent evidence indicates that thrombolysis may be an effective therapy for the treatment of acute ischemic stroke. However, the reperfusion of ischemic brain comes with a price. In clinical trials, patients treated with thrombolytic therapy have shown a 6% rate of intracerebral hemorrhage, which was balanced against a 30% improvement in functional outcome over controls. Destruction of the microvasculature and extension of the infarct area occur after cerebral reperfusion. We have reviewed the existing data indicating that an inflammatory response occurring after the reestablishment of circulation has a causative role in this reperfusion injury. The recruitment of neutrophils to the area of ischemia, the first step to inflammation, involves the coordinated appearance of multiple proteins. Intercellular adhesion molecule-1 and integrins are adhesion molecules that are up-regulated in endothelial cells and leukocytes. Tumor necrosis factor-alpha, interleukin-1, and platelet-activating factor also participate in leukocyte accumulation and subsequent activation. Therapies that interfere with the functions of these factors have shown promise in reducing reperfusion injury and infarct extension in the experimental setting. They may prove to be useful adjuncts to thrombolytic therapy in the treatment of acute ischemic stroke.
authors.affiliation: Department of Neurosurgery, University of Minnesota, Minneapolis 55455, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Jean
authors.forename: S R
authors.initials: SR
authors.lastname: Spellman
authors.forename: E S
authors.initials: ES
authors.lastname: Nussbaum
authors.forename: W C
authors.initials: WC
authors.lastname: Low
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D002448:Cell Adhesion / Q000187:drug effects; D002543:Cerebral Hemorrhage / Q000139:chemically induced; D002634:Chemotaxis, Leukocyte; D016264:Dextran Sulfate / Q000627:therapeutic use; D004285:Dogs; D004660:Encephalitis / Q000188:drug therapy / Q000209:etiology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005343:Fibrinolytic Agents / Q000009:adverse effects; D006801:Humans; D016023:Integrins / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007375:Interleukin-1 / Q000502:physiology; D051379:Mice; D018696:Neuroprotective Agents / Q000627:therapeutic use; D009504:Neutrophils / Q000502:physiology; D010215:Papio; D010587:Phagocytosis; D010972:Platelet Activating Factor / Q000502:physiology; D011817:Rabbits; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D015912:Thrombolytic Therapy / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D000893:Anti-Inflammatory Agents; D005343:Fibrinolytic Agents; D016023:Integrins; D007375:Interleukin-1; D018696:Neuroprotective Agents; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016264:Dextran Sulfate