Tissue factor contributes to microvascular defects after focal cerebral ischemia

Winston S. Thomas, Etsuro Mori, Brian R. Copeland, Jian Qing Yu, James H. Morrissey, Gregory J. del Zoppo

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81 Citations (Scopus)


Background and Purpose: Microvascular perfusion defects occur after occlusion and reperfusion of the middle cerebral artery in examples of focal cerebral ischemia. In addition to cellular (eg, polymorpho-nuclear leukocyte) contributors to the focal “no-reflow” phenomenon, activation of coagulation may also play a role. We have tested a potential role of tissue factor-mediated coagulation in the microvascular perfusion defects seen after focal cerebral ischemia-reperfusion in a baboon model of reversible middle cerebral artery occlusion with the murine anti-tissue factor monoclonal antibody TF9-6B4. Tissue factor is the principal resident procoagulant substance in cerebral tissues and has a distinct perivascular distribution. Methods: Microvascular patency in the basal ganglia after 3-hour middle cerebral artery occlusion and 1-hour reperfusion was quantified by computerized video imaging of carbon-tracer perfused tissues. Animals were randomized to receive intravenous TF9-6B4 (10 mg/kg) 10 minutes before middle cerebral artery occlusion (n=6) or no treatment (n=6) in an open study. Results: In the control animals, a significant decrease in patency was confirmed in microvessels less than 30,μm in diameter. Infusion of TF9-6B4 before middle cerebral artery occlusion produced a stable maximal level of circulating antibody within 10 minutes, which lasted the duration of ischemia and reperfusion. An increase in reflow in microvessels of all size classes occurred after TF9-6B4 infusion, which was significant in those 7.5 to 30 μm (P=.038) and 30 to 50,μm (P=.013) in diameter. Conclusions: These results indicate that tissue factor-mediated events may also contribute to no-reflow in noncapillary microvessels after focal cerebral ischemia.

Original languageEnglish
Pages (from-to)847-853
Number of pages7
Issue number6
Publication statusPublished - 1993 Jun


  • Baboons
  • Cerebral ischemia
  • Microcirculation
  • Procoagulant

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing


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