Show simple item record

dc.contributor.authorAtkinson, Wendy
dc.contributor.authorForghani, Reza
dc.contributor.authorWojtkiewicz, Gregory R.
dc.contributor.authorPulli, Benjamin
dc.contributor.authorIwamoto, Yoshiko
dc.contributor.authorUeno, Takuya
dc.contributor.authorWaterman, Peter
dc.contributor.authorTruelove, Jessica
dc.contributor.authorOklu, Rahmi
dc.contributor.authorChen, John Wen-Yueh
dc.date.accessioned2013-02-20T18:25:55Z
dc.date.issued2012
dc.identifier.citationAtkinson, 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.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10318210
dc.description.abstractAn 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.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0033671en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310075/pdf/en_US
dash.licenseLAA
dc.subjectbiologyen_US
dc.subjectimmunologyen_US
dc.subjectimmunityen_US
dc.subjectmodel organismsen_US
dc.subjectanimal modelsen_US
dc.subjectmedicineen_US
dc.subjectclinical immunologyen_US
dc.subjectneurologyen_US
dc.subjectdemyelinating disordersen_US
dc.subjectradiologyen_US
dc.subjectveterinary scienceen_US
dc.subjectanimal typesen_US
dc.titleLigation of the Jugular Veins Does Not Result in Brain Inflammation or Demyelination in Miceen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorOklu, Rahmi
dc.date.available2013-02-20T18:25:55Z
dc.identifier.doi10.1371/journal.pone.0033671*
dash.contributor.affiliatedPulli, Benjamin
dash.contributor.affiliatedForghani, Reza
dash.contributor.affiliatedUeno, Takuya
dash.contributor.affiliatedOklu, Rahmi
dash.contributor.affiliatedChen, John


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record