Coadministration of low-dose lipopolysaccharide and soluble tissue factor induces thrombosis after radiosurgery in an animal arteriovenous malformation model

Kingsley Storer, Jian Tu, Athula Karunanayaka, Robert Smee, Richard Short, Philip Thorpe, Marcus Stoodley

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

OBJECTIVE: Radiosurgery for arteriovenous malformations is limited to small lesions and may take 3 years to produce total occlusion. It has recently been shown that coadministration of low-dose lipopolysaccharide (LPS) and soluble tissue factor (sTF) selectively induces thrombosis in murine tumor models, attributable perhaps to the prothrombotic phenotype of tumor vasculature. Radiosurgery may induce changes in endothelial prothrombotic molecules similar to those found in tumors. This study aimed to determine if a similar strategy could be used to stimulate thrombus formation in an animal arteriovenous malformation model. METHODS: Seventeen rats underwent creation of a carotid-to-jugular anastomosis. Animals were intravenously injected with sTF, low-dose LPS, a combination of both, or placebo 24 hours after stereotactic irradiation of the anastomosis. Control animals received both agents after sham irradiation. RESULTS: Coadministration of sTF and LPS led to the formation of thrombi in up to 69% of small vessels and 39% of medium-sized vessels within the target region. The irradiated vasculature demonstrated intermediate rates of thrombosis after treatment with either sTF or LPS alone as did vessels within the fistula in the control group. Logistic regression analysis demonstrated significant associations between development of thrombi and treatment with radiation, sTF, or LPS (P < 0.005). There was no evidence of systemic thrombus formation or toxicity in any group. CONCLUSION: Treatment with sTF and LPS selectively induces thrombosis of irradiated vessels in a rat model of arteriovenous malformation. Stimulation of thrombosis may improve the efficacy of radiosurgery, increasing the treatable lesion size and reducing latency.

Original languageEnglish (US)
Pages (from-to)604-610
Number of pages7
JournalNeurosurgery
Volume61
Issue number3
DOIs
StatePublished - Sep 1 2007

Keywords

  • Inducing thrombosis postradiosurgery
  • Intracranial arteriovenous malformations
  • Lipopolysaccharides
  • Radiosurgery
  • Tissue factor

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Coadministration of low-dose lipopolysaccharide and soluble tissue factor induces thrombosis after radiosurgery in an animal arteriovenous malformation model'. Together they form a unique fingerprint.

Cite this