Clot injection technique affects thrombolytic efficacy in a rat embolic stroke model: implications for translaboratory collaborations
Biochemistry & Molecular Pharmacology
Department of Neurology; Department of Radiology
Medical Subject Headings
Animals; Cerebrovascular Circulation; *Clinical Laboratory Techniques; Cooperative Behavior; *Disease Models, Animal; Fibrinolytic Agents; Infarction, Middle Cerebral Artery; Injections, Intra-Arterial; Intracranial Embolism; Male; Rats; Rats, Inbred WKY; Stroke; Tissue Plasminogen Activator; Treatment Outcome
Nervous System Diseases | Neurology | Radiology
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.
Rights and Permissions
Citation: J Cereb Blood Flow Metab. 2014 Apr;34(4):677-82. doi: 10.1038/jcbfm.2014.1. Epub 2014 Jan 15. Link to article on publisher's site
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
Marinescu, Marilena; Bouley, James P.; Chueh, Juyu; Fisher, Marc; and Henninger, Nils, "Clot injection technique affects thrombolytic efficacy in a rat embolic stroke model: implications for translaboratory collaborations" (2014). GSBS Student Publications. 1908.