Blood-brain barrier disruption in CCL2 transgenic mice during pertussis toxin-induced brain inflammation

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dc.contributor.authorSchellenberg, Angela E
dc.contributor.authorBuist, Richard
dc.contributor.authorDel Bigio, Marc R
dc.contributor.authorToft-Hansen, Henrik
dc.contributor.authorKhorooshi, Reza
dc.contributor.authorOwens, Trevor
dc.contributor.authorPeeling, James
dc.date.accessioned2012-08-17T19:16:20Z
dc.date.available2012-08-17T19:16:20Z
dc.date.issued2012-04-30
dc.date.updated2012-08-17T19:16:20Z
dc.description.abstractAbstract Background The chemokine CCL2 has an important role in the recruitment of inflammatory cells into the central nervous system (CNS). A transgenic mouse model that overexpresses CCL2 in the CNS shows an accumulation of leukocytes within the perivascular space surrounding vessels, and which infiltrate into the brain parenchyma following the administration of pertussis toxin (PTx). Methods This study used contrast-enhanced magnetic resonance imaging (MRI) to quantify the extent of blood–brain barrier (BBB) disruption in this model pre- and post-PTx administration compared to wild-type mice. Contrast-enhanced MR images were obtained before and 1, 3, and 5 days after PTx injection in each animal. After the final imaging session fluorescent dextran tracers were administered intravenously to each mouse and brains were examined histologically for cellular infiltrates, BBB leakage and tight junction protein. Results BBB breakdown, defined as a disruption of both the endothelium and glia limitans, was found only in CCL2 transgenic mice following PTx administration and seen on MR images as focal areas of contrast enhancement and histologically as dextrans leaking from blood vessels. No evidence of disruption in endothelial tight junctions was observed. Conclusion Genetic and environmental stimuli were needed to disrupt the integrity of the BBB in this model of neuroinflammation.
dc.description.versionPeer Reviewed
dc.identifier.citationFluids and Barriers of the CNS. 2012 Apr 30;9(1):10
dc.identifier.doihttp://dx.doi.org/10.1186/2045-8118-9-10
dc.identifier.urihttp://hdl.handle.net/1993/8358
dc.language.rfc3066en
dc.rightsopen accessen_US
dc.rights.holderAngela E Schellenberg et al.; licensee BioMed Central Ltd.
dc.titleBlood-brain barrier disruption in CCL2 transgenic mice during pertussis toxin-induced brain inflammation
dc.typeJournal Article
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