Temporal profile of enhanced vulnerability of the postthrombotic brain to secondary embolic events

Gary Danton, Ricardo Prado, Brant D. Watson, W. Dalton Dietrich

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1113-1119
Number of pages7
JournalStroke
Volume33
Issue number4
DOIs
StatePublished - Apr 20 2002

Fingerprint

Carotid Artery Thrombosis
Brain
Stroke
Embolism
Vascular Diseases
Infarction
Heart Diseases
Thrombosis
Blood Platelets
Hemodynamics
Outcome Assessment (Health Care)

Keywords

  • Cerebral infarction
  • Ischemic attack, transient
  • Ischemic preconditioning
  • Platelet aggregation
  • Rats

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Temporal profile of enhanced vulnerability of the postthrombotic brain to secondary embolic events. / Danton, Gary; Prado, Ricardo; Watson, Brant D.; Dalton Dietrich, W.

In: Stroke, Vol. 33, No. 4, 20.04.2002, p. 1113-1119.

Research output: Contribution to journalArticle

@article{7e6a27a688f94b5298cbbd5fcc96e516,
title = "Temporal profile of enhanced vulnerability of the postthrombotic brain to secondary embolic events",
abstract = "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.",
keywords = "Cerebral infarction, Ischemic attack, transient, Ischemic preconditioning, Platelet aggregation, Rats",
author = "Gary Danton and Ricardo Prado and Watson, {Brant D.} and {Dalton Dietrich}, W.",
year = "2002",
month = "4",
day = "20",
doi = "10.1161/hs0402.105554",
language = "English",
volume = "33",
pages = "1113--1119",
journal = "Stroke",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Temporal profile of enhanced vulnerability of the postthrombotic brain to secondary embolic events

AU - Danton, Gary

AU - Prado, Ricardo

AU - Watson, Brant D.

AU - Dalton Dietrich, W.

PY - 2002/4/20

Y1 - 2002/4/20

N2 - 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.

AB - 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.

KW - Cerebral infarction

KW - Ischemic attack, transient

KW - Ischemic preconditioning

KW - Platelet aggregation

KW - Rats

UR - http://www.scopus.com/inward/record.url?scp=0036218941&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036218941&partnerID=8YFLogxK

U2 - 10.1161/hs0402.105554

DO - 10.1161/hs0402.105554

M3 - Article

VL - 33

SP - 1113

EP - 1119

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 4

ER -