title: A novel atherothrombotic model of ischemic stroke induced by injection of collagen into the cerebral vasculature.
abstract: BACKGROUND
  Most ischemic strokes in humans are caused by ruptured arterial atheroma, which activate platelets and produce thrombi that occlude cerebral vessels.
  
  
  METHODS
  To simulate these events, we threaded a catheter through the internal carotid artery toward the middle cerebral artery (MCA) orifice and injected collagen directly into the cerebral circulation of male C57Bl/6 mice and Wistar rats.
  
  
  RESULTS
  Laser-Doppler flowmetry demonstrated reductions in cerebral blood flow (CBF) of ∼80% in mice and ∼60% in rats. CBF spontaneously increased but remained depressed after catheter withdrawal. Magnetic resonance imaging showed that ipsilateral CBF was reduced at 3h after collagen injection and markedly improved at 48 h. Micro-computed tomography revealed reduced blood vessel density in the ipsilateral MCA territory at 3 h. Gross examination of excised brains revealed thrombi within ipsilateral cerebral arteries at 3 h, but not 24 h, after collagen injection. Immunofluorescence microscopy confirmed that platelets and fibrinogen/fibrin were major components of these thrombi at both macrovascular and microvascular levels. Cerebral infarcts comprising ∼30% of hemispheric volume and neurobehavioral deficits were observed 48 h after ischemic injury in both mice and rats.
  
  
  METHODS
  Collagen injection caused brain injury that was similar in magnitude and variability to mechanical MCA occlusion or injection of a pre-formed clot; however, alterations in CBF and the mechanism of vascular occlusion were more consistent with clinical ischemic stroke.
  
  
  CONCLUSIONS
  This novel rodent model of ischemic stroke has pathophysiologic characteristics consistent with clinical atherothrombotic stroke, is technically feasible, and creates reproducible brain injury.
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Schunke
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Toung
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The Russell H. Morgan Department of Radiology & Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Arvind P
authors.initials: AP
authors.lastname: Pathak
authors.affiliation: F. M. Kirby Functional Imaging Center, Kennedy Krieger Institute, Baltimore, MD, USA.
authors.forename: Jiadi
authors.initials: J
authors.lastname: Xu
authors.affiliation: The Russell H. Morgan Department of Radiology & Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Jiangyang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Koehler
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: nfaraday@jhmi.edu.
authors.forename: Nauder
authors.initials: N
authors.lastname: Faraday
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000139:chemically induced; D002545:Brain Ischemia / Q000139:chemically induced* / Q000150:complications*; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D003094:Collagen / Q000633:toxicity*; D004195:Disease Models, Animal; D007839:Functional Laterality; D017078:Laser-Doppler Flowmetry; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009422:Nervous System Diseases / Q000209:etiology; D009504:Neutrophils / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D020521:Stroke / Q000150:complications / Q000209:etiology* / Q000473:pathology; D013997:Time Factors; D014057:Tomography, X-Ray Computed
chemical_list: D003094:Collagen
keywords: Atherothrombosis; Collagen; Ischemic stroke; Mouse; Platelet; Rat