Regular ArticleTransient ischemia elicits a sustained enhancement of thrombus development in the cerebral microvasculature: Effects of anti-thrombotic therapy

- Cerebral microvascular thrombus formation was evaluated after ischemia (2-10 min).
- The rate of thrombus formation was accelerated following brain ischemia.
- The accelerated thrombogenesis was evident up to 28 days after ischemia.
- Antiplatelet and antithrombotic agents did not blunt this response to ischemia.

ObjectiveWhile 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 & resultsThe middle cerebral artery of C57BL/6 mice was occluded for 2.5-10 min, followed by reperfusion periods of 1-28 days. 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 1 day), it yielded a pronounced and prolonged (up to 28 days) 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.ConclusionsThe 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.