title: A novel mouse model of thromboembolic stroke.
abstract: BACKGROUND
  We previously demonstrated that tissue plasminogen activator (tPA) reduces infarct size after mechanical middle cerebral artery occlusion (MCAO) in wild-type (WT) mice and transgenic mice expressing human leukocyte antigen DR2 (DR2-Tg). Clinically, tPA limits ischemic damage by dissolving the clot blocking blood flow through a cerebral artery. To mimic the clinical situation, we developed a new mouse model of thromboembolic stroke, and tested the efficacy of tPA in WT and DR2-Tg mice. New Method Autologous blood is withdrawn into a PE-8 catheter filled with 2 IU α-thrombin. After exposing the catheter briefly to air, the catheter is reintroduced into the external (ECA) and advanced into the internal carotid artery (ICA) to allow for intravascular injection of thrombin at the MCA bifurcation. To validate the model, we tested the effect of tPA on laser-Doppler perfusion (LDP) over the MCA territory and infarct size in WT and DR2-Tg mice.
  
  
  RESULTS
  The procedure results in a consistent drop in LDP, and leads to a highly reproducible ischemic lesion. When administered at 15min after thrombosis, tPA restored LDP and resulted in a significant reduction in infarct size at 24h after thrombosis in both WT and DR2-Tg.
  
  
  METHODS
  Our model significantly reduces surgery time, requires a single anesthesia exposure, and produces a consistent and predictable infarction, with low variability and mortality.
  
  
  CONCLUSIONS
  We validated the efficacy of tPA in restoring blood flow and reducing infarct in a new model of endovascular thromboembolic stroke in the mouse.
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Wenri
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Libal
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Murphy
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA; Department of Neurology, Oregon Health & Science University, Portland, OR, USA; Neuroimmunology Research, Portland VA Medical Center, Portland, OR, USA.
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA; Department of Neurology, Oregon Health & Science University, Portland, OR, USA; Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA. Electronic address: alkayedn@ohsu.edu.
authors.forename: Nabil J
authors.initials: NJ
authors.lastname: Alkayed
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D020766:Intracranial Embolism / Q000188:drug therapy / Q000473:pathology; D020767:Intracranial Thrombosis / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019635:Neurosurgical Procedures / Q000379:methods; D011897:Random Allocation; D020521:Stroke / Q000188:drug therapy / Q000473:pathology; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: Cerebral ischemia; Mouse; Optical microangiography; Stroke, Thromboembolic; tPA