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(Stroke. 2002;33:1113.)
© 2002 American Heart Association, Inc.

Original Contributions

Temporal Profile of Enhanced Vulnerability of the Postthrombotic Brain to Secondary Embolic Events

Gary H. Danton, BS; Ricardo Prado, MD; Brant D. Watson, PhD W. Dalton Dietrich, PhD

From the Departments of Neurological Surgery (G.H.D., W.D.D.) and Neurology (R.P., B.D.W., W.D.D.), The Miami Project to Cure Paralysis (G.H.D., W.D.D.), and Neuroscience Program (G.H.D., B.D.W., W.D.D.), University of Miami School of Medicine (Fla).

Correspondence to W. Dalton Dietrich, PhD, The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami School of Medicine, Lois Pope Life Center, PO Box 016960 (R-48), Miami, FL 33101. E-mail ddietrich@ miami.edu

Background and Purpose— Patients with vascular or cardiac disease may experience recurrent thrombosis and embolization to the cerebral vasculature. Transient distal platelet accumulation after common carotid artery thrombosis (CCAT) leads to hemodynamic, metabolic, and molecular events that may influence the response of the postthromboembolic brain to secondary emboli. We investigated the effect of repeated embolic episodes on histopathological outcome at various time intervals using a clinically relevant model of embolic stroke.

Methods— Six groups of rats underwent either photochemically induced CCAT followed by sham surgery or 2 episodes of CCAT separated by 10 minutes or 1, 3, 5, or 7 days. Outcome measures included routine histopathological analysis and determination of the number of infarct loci and their total volume.

Results— Rats that underwent a second CCAT at 1, 3, or 5 days after the first insult had 20 to 30 times larger infarct volumes than rats in the single-CCAT group (P<0.05). In addition, rats in the 10-minute and 1-, 3-, and 5-day groups had 2 to 3 times as many infarcts as those in the single-CCAT group (P<0.05). Infarcts produced by double insults commonly extended through the neuraxis and were necrotic, edematous, and sometimes hemorrhagic.

Conclusions— A prior thromboembolic event puts the brain at risk for severe infarction after a second embolic event. These findings cannot be explained solely by a greater number of infarcts. Elucidating pathomechanisms responsible for the vulnerability of the postthromboembolic brain may provide targets for new treatment strategies to prevent the severe consequences of embolic stroke.

Key Words: cerebral infarction • ischemic attack, transient • ischemic preconditioning • platelet aggregation • rats

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