title: Transient ischemia elicits a sustained enhancement of thrombus development in the cerebral microvasculature: effects of anti-thrombotic therapy.
abstract: OBJECTIVE
  While transient ischemic attack (TIA) is a well-known harbinger of ischemic stroke, the mechanisms that link TIA to subsequent strokes remain poorly understood. The overall aim of this study was to determine whether: 1) brief periods of transient cerebral ischemia render this tissue more vulnerable to thrombus development and 2) antiplatelet agents used in TIA patients alter ischemia-induced thrombogenesis.
  
  
  RESULTS
  The middle cerebral artery of C57BL/6 mice was occluded for 2.5-10min, followed by reperfusion periods of 1-28days. Intravital microscopy was used to monitor thrombus development in cerebral microvessels induced by light/dye photoactivation. Thrombosis was quantified as the time to platelet aggregation on the vessel wall and the time for complete blood flow cessation. While brief periods of cerebral ischemia were not associated with neurological deficits or brain infarction (evaluated after 1day), it yielded a pronounced and prolonged (up to 28days) acceleration of thrombus formation, compared to control (sham) mice. This prothrombotic phenotype was not altered by pre- and/or post-treatment of mice with either aspirin (A), clopidogrel (C), dipyridamole (D), or atorvastatin (S), or with A+D+S.
  
  
  CONCLUSIONS
  The increased vulnerability of the cerebral vasculature to thrombus development after a brief period of transient ischemia can be recapitulated in a murine model. Antiplatelet or antithrombotic agents used in patients with TIA show no benefit in this mouse model of brief transient ischemia.
authors: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors: Ya Hui
authors: YH
authors: Tang
authors: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors: Shantel
authors: S
authors: Vital
authors: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors: Janice
authors: J
authors: Russell
authors: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors: Hilary
authors: H
authors: Seifert
authors: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors: Elena
authors: E
authors: Senchenkova
authors: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA. Electronic address: dgrang@lsuhsc.edu.
authors: D Neil
authors: DN
authors: Granger
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000209:etiology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005340:Fibrinogen / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology*; D020767:Intracranial Thrombosis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018715:Microscopy, Video; D055806:Microvessels / Q000187:drug effects / Q000503:physiopathology*; D009460:Neurologic Examination; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D005343:Fibrinolytic Agents; D019038:Platelet Glycoprotein GPIb-IX Complex; D005340:Fibrinogen
keywords: Aspirin; Clopidogrel; Dipyridamole; Statin; Thrombosis; Transient ischemic attack