title: Blood-brain barrier disruption in CCL2 transgenic mice during pertussis toxin-induced brain inflammation.
abstract: 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.
  
  
  CONCLUSIONS
  Genetic and environmental stimuli were needed to disrupt the integrity of the BBB in this model of neuroinflammation.
authors.affiliation: Department of Pharmacology & Therapeutics, University of Manitoba, 753 McDermot Avenue, Winnipeg, Manitoba, R3E 0T6, Canada. aes146@mail.usask.ca.
authors.forename: Angela E
authors.initials: AE
authors.lastname: Schellenberg
authors.forename: Richard
authors.initials: R
authors.lastname: Buist
authors.forename: Marc R
authors.initials: MR
authors.lastname: Del Bigio
authors.forename: Henrik
authors.initials: H
authors.lastname: Toft-Hansen
authors.forename: Reza
authors.initials: R
authors.lastname: Khorooshi
authors.forename: Trevor
authors.initials: T
authors.lastname: Owens
authors.forename: James
authors.initials: J
authors.lastname: Peeling