Thromboembolic events predispose the brain to widespread cerebral infarction after delayed transient global ischemia in rats

W. Dalton Dietrich, Gary Danton, Aviva C. Hopkins, Ricardo Prado

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Background and Purpose-Transient distal platelet accumulation after common carotid artery thrombosis (CCAT) leads to hemodynamic, metabolic, and molecular events that may influence the response of the postthrombotic brain to secondary insults. We investigated how a thromboembolic insult would affect histopathological outcome when combined with an ischemic insult induced 24 hours later. Methods-Three groups of rats underwent either (1) CCAT+10 minutes of normothermic 2-vessel occlusion (n=6), (2) CCAT+sham ischemia procedures (n=6), or (3) sham CCAT procedures+10 minutes of 2- vessel occlusion (n=6). At 7 days, rats were perfused for quantitative histopathological and immunocytochemical analysis. Results-Rats undergoing combined insults (group 1) had significantly larger areas of ischemic injury (P<0.05) within the cerebral cortex, striatum, and thalamus compared with the other, single-injury groups. Increased ischemic damage included selective neuronal necrosis, infarction, and focal hemorrhage. By means of glial fibrillary acidic protein immunocytochemistry and lectin histochemistry, reactive astrocytes and microglia were found to be associated with widespread tissue necrosis. In contrast, infrequent infarction or CA1 hippocampal neuronal necrosis was observed in groups 2 and 3, respectively. Conclusions- A prior thromboembolic event is a risk factor for widespread cerebral infarction and hemorrhage when combined with a delayed ischemic insult. The understanding of what factors enhance the susceptibility of the postthrombotic brain to secondary insults may aid in the development of neuroprotective strategies to be applied after transient ischemic attacks to prevent the initiation of stroke.

Original languageEnglish (US)
Pages (from-to)855-862
Number of pages8
JournalStroke
Volume30
Issue number4
DOIs
StatePublished - Apr 1999

Keywords

  • Astrocytes
  • Cerebral infarction
  • Microglia
  • Platelets
  • Rats
  • Risk factors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

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