Ligation of the Jugular Veins Does Not Result in Brain Inflammation or Demyelination in Mice

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Ligation of the Jugular Veins Does Not Result in Brain Inflammation or Demyelination in Mice

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Title: Ligation of the Jugular Veins Does Not Result in Brain Inflammation or Demyelination in Mice
Author: Atkinson, Wendy; Wojtkiewicz, Gregory R.; Iwamoto, Yoshiko; Waterman, Peter; Truelove, Jessica; Forghani, Reza; Pulli, Benjamin; Ueno, Takuya; Oklu, Rahmi; Chen, John Wen-Yueh

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Citation: Atkinson, Wendy, Reza Forghani, Gregory R. Wojtkiewicz, Benjamin Pulli, Yoshiko Iwamoto, Takuya Ueno, Peter Waterman, Jessica Truelove, Rahmi Oklu, and John W. Chen. 2012. Ligation of the jugular veins does not result in brain inflammation or demyelination in mice. PLoS ONE 7(3): e33671.
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Abstract: An alternative hypothesis has been proposed implicating chronic cerebrospinal venous insufficiency (CCSVI) as a potential cause of multiple sclerosis (MS). We aimed to evaluate the validity of this hypothesis in a controlled animal model. Animal experiments were approved by the institutional animal care committee. The jugular veins in SJL mice were ligated bilaterally (n = 20), and the mice were observed for up to six months after ligation. Sham-operated mice (n = 15) and mice induced with experimental autoimmune encephalomyelitis (n = 8) were used as negative and positive controls, respectively. The animals were evaluated using CT venography and 99mTc-exametazime to assess for structural and hemodynamic changes. Imaging was performed to evaluate for signs of blood-brain barrier (BBB) breakdown and neuroinflammation. Flow cytometry and histopathology were performed to assess inflammatory cell populations and demyelination. There were both structural changes (stenosis, collaterals) in the jugular venous drainage and hemodynamic disturbances in the brain on \(^{99m}\)Tc-exametazime scintigraphy (p = 0.024). In the JVL mice, gadolinium MRI and immunofluorescence imaging for barrier molecules did not reveal evidence of BBB breakdown (p = 0.58). Myeloperoxidase, matrix metalloproteinase, and protease molecular imaging did not reveal signs of increased neuroinflammation (all p>0.05). Flow cytometry and histopathology also did not reveal increase in inflammatory cell infiltration or population shifts. No evidence of demyelination was found, and the mice remained without clinical signs. Despite the structural and hemodynamic changes, we did not identify changes in the BBB permeability, neuroinflammation, demyelination, or clinical signs in the JVL group compared to the sham group. Therefore, our murine model does not support CCSVI as a cause of demyelinating diseases such as multiple sclerosis.
Published Version: doi:10.1371/journal.pone.0033671
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