Ya Hui Tang1, Shantel Vital1, Janice Russell1, Hilary Seifert1, Elena Senchenkova1, D Neil Granger2. 1. Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA. 2. Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA. Electronic address: dgrang@lsuhsc.edu.
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. APPROACH & 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.
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. APPROACH & 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: J Donald Easton; Jeffrey L Saver; Gregory W Albers; Mark J Alberts; Seemant Chaturvedi; Edward Feldmann; Thomas S Hatsukami; Randall T Higashida; S Claiborne Johnston; Chelsea S Kidwell; Helmi L Lutsep; Elaine Miller; Ralph L Sacco Journal: Stroke Date: 2009-05-07 Impact factor: 7.914
Authors: T F Choudhri; B L Hoh; H G Zerwes; C J Prestigiacomo; S C Kim; E S Connolly; G Kottirsch; D J Pinsky Journal: J Clin Invest Date: 1998-10-01 Impact factor: 14.808
Authors: J Eileen Bird; Xinkang Wang; Patricia L Smith; Frank Barbera; Christine Huang; William A Schumacher Journal: J Thromb Thrombolysis Date: 2012-08 Impact factor: 2.300
Authors: Scarlett Gillespie; Paul M Holloway; Felix Becker; Francesca Rauzi; Shantel A Vital; Kirk A Taylor; Karen Y Stokes; Michael Emerson; Felicity N E Gavins Journal: Br J Pharmacol Date: 2018-07-03 Impact factor: 8.739
Authors: Rebecca D Steubing; Fabian Szepanowski; Christina David; Ayan Mohamud Yusuf; Stine Mencl; Anne-Kathrin Mausberg; Harald F Langer; Manuela Sauter; Cornelius Deuschl; Michael Forsting; Anke C Fender; Dirk M Hermann; Ana I Casas; Friederike Langhauser; Christoph Kleinschnitz Journal: Brain Behav Immun Health Date: 2022-07-21