title: Complement depletion does not reduce brain injury in a rabbit model of thromboembolic stroke.
abstract: The contribution of the complement system to cerebral ischemic and ischemia/reperfusion injury was examined in a rabbit model of thromboembolic stroke by delivery of an autologous clot embolus to the intracranial circulation via the internal carotid artery. A two-by-two factorial design was employed to study the impact of complement depletion via pretreatment with cobra venom factor (CVF, 100 U/kg i.v.) in the setting of permanent (without tissue plasminogen activator; t-PA) and transient (with t-PA) cerebral ischemia. Thirty-two New Zealand white rabbits were assigned to one of four groups (n=8, each group): control without t-PA, control with t-PA, CVF without t-PA and CVF with t-PA. In the complement intact animals, t-PA administration resulted in an approximate 30% reduction in infarct size when compared to the group not receiving t-PA (20.4+/-6.6% of hemisphere area vs. 30.1+/-7.2%; mean+/-SEM). However, infarct sizes in the complement depleted rabbits, with (30.7+/-8.2%) or without (30.2+/-7.9%) t-PA, were no different from the control group receiving no therapy. Similarly, no difference in regional cerebral blood flow or final intracranial pressure values was noted between any of the four groups. Complement activation does not appear to be a primary contributor to brain injury in acute thromboembolic stroke.
authors.affiliation: Department of Pharmacology, University of Vermont, Burlington 05405, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Lew
authors.forename: C E
authors.initials: CE
authors.lastname: Gross
authors.forename: M M
authors.initials: MM
authors.lastname: Bednar
authors.forename: S J
authors.initials: SJ
authors.lastname: Russell
authors.forename: S P
authors.initials: SP
authors.lastname: Fuller
authors.forename: C L
authors.initials: CL
authors.lastname: Ellenberger
authors.forename: D
authors.initials: D
authors.lastname: Howard
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000201:enzymology; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000378:metabolism*; D050577:Complement C3-C5 Convertases / Q000378:metabolism; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D003165:Complement System Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000494:pharmacology; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology; D002542:Intracranial Embolism and Thrombosis / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000502:physiology; D011817:Rabbits; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
chemical_list: D003169:Complement Inactivator Proteins; D004546:Elapid Venoms; D005343:Fibrinolytic Agents; C016310:cobra venom factor; D003165:Complement System Proteins; D050577:Complement C3-C5 Convertases; D010959:Tissue Plasminogen Activator