title: Clot injection technique affects thrombolytic efficacy in a rat embolic stroke model: implications for translaboratory collaborations.
abstract: Current recommendations encourage the use of embolic stroke (ES) models and replication of results across laboratories in preclinical research. Since such endeavors employ different surgeons, we sought to ascertain the impact of injection technique on outcome and response to thrombolysis in an ES model. Embolic stroke was induced in Male Wistar Kyoto rats (n=166) by a fast or a slow clot injection (CI) technique. Saline or recombinant tissue plasminogen activator (rtPA) was given at 1 hour after stroke. Flow rate curves were assessed in 24 animals. Cerebral perfusion was assessed using laser Doppler flowmetry. Edema corrected infarct volume, hemispheric swelling, hemorrhagic transformation, and neurologic outcome were assessed at 24 hours after stroke. Clot burden was estimated in a subset of animals (n=40). Slow CI resulted in significantly smaller infarct volumes (P=0.024) and better neurologic outcomes (P=0.01) compared with fast CI at 24 hours. Unexpectedly, rtPA treatment attenuated infarct size in fast (P<0.001) but not in slow CI experiments (P=0.382), possibly related to reperfusion injury as indicated by greater hemorrhagic transformation (P<0.001) and hemispheric swelling (P<0.05). Outcome and response to thrombolysis after ES are operator dependent, which needs to be considered when comparing results obtained from different laboratories.
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Marilena
authors.initials: M
authors.lastname: Marinescu
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: James
authors.initials: J
authors.lastname: Bouley
authors.affiliation: Department of Radiology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Juyu
authors.initials: J
authors.lastname: Chueh
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Fisher
authors.affiliation: 1] Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, USA [2] Department of Psychiatry, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Nils
authors.initials: N
authors.lastname: Henninger
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects; D019411:Clinical Laboratory Techniques / Q000379:methods / Q000592:standards; D003299:Cooperative Behavior; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D007269:Injections, Intra-Arterial; D020766:Intracranial Embolism / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D020521:Stroke / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator