title: Exposure to vehicle emissions results in altered blood brain barrier permeability and expression of matrix metalloproteinases and tight junction proteins in mice.
abstract: BACKGROUND
  Traffic-generated air pollution-exposure is associated with adverse effects in the central nervous system (CNS) in both human exposures and animal models, including neuroinflammation and neurodegeneration. While alterations in the blood brain barrier (BBB) have been implicated as a potential mechanism of air pollution-induced CNS pathologies, pathways involved have not been elucidated.
  
  
  OBJECTIVE
  To determine whether inhalation exposure to mixed vehicle exhaust (MVE) mediates alterations in BBB permeability, activation of matrix metalloproteinases (MMP) -2 and -9, and altered tight junction (TJ) protein expression.
  
  
  METHODS
  Apolipoprotein (Apo) E(-/-) and C57Bl6 mice were exposed to either MVE (100 μg/m(3) PM) or filtered air (FA) for 6 hr/day for 30 days and resulting BBB permeability, expression of ROS, TJ proteins, markers of neuroinflammation, and MMP activity were assessed. Serum from study mice was applied to an in vitro BBB co-culture model and resulting alterations in transport and permeability were quantified.
  
  
  RESULTS
  MVE-exposed Apo E(-/-) mice showed increased BBB permeability, elevated ROS and increased MMP-2 and -9 activity, compared to FA controls. Additionally, cerebral vessels from MVE-exposed mice expressed decreased levels of TJ proteins, occludin and claudin-5, and increased levels of inducible nitric oxide synthase (iNOS) and interleukin (IL)-1β in the parenchyma. Serum from MVE-exposed animals also resulted in increased in vitro BBB permeability and altered P-glycoprotein transport activity.
  
  
  CONCLUSIONS
  These data indicate that inhalation exposure to traffic-generated air pollutants promotes increased MMP activity and degradation of TJ proteins in the cerebral vasculature, resulting in altered BBB permeability and expression of neuroinflammatory markers.
authors.forename: Hannah A
authors.initials: HA
authors.lastname: Oppenheim
authors.forename: JoAnn
authors.initials: J
authors.lastname: Lucero
authors.forename: Anne-Cécile
authors.initials: AC
authors.lastname: Guyot
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Herbert
authors.forename: Jacob D
authors.initials: JD
authors.lastname: McDonald
authors.forename: Aloïse
authors.initials: A
authors.lastname: Mabondzo
authors.affiliation: Environmental Respiratory Health Program, Lovelace Respiratory Research Institute, Albuquerque, NM,USA. amie.lund@unt.edu.
authors.forename: Amie K
authors.initials: AK
authors.lastname: Lund
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000097:blood; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D015153:Blotting, Western; D002199:Capillary Permeability / Q000187:drug effects*; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019570:Inhalation Exposure / Q000009:adverse effects*; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020078:Neurogenic Inflammation / Q000097:blood / Q000139:chemically induced / Q000201:enzymology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D062725:Tight Junction Proteins / Q000235:genetics*; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001057:Apolipoproteins E; D062725:Tight Junction Proteins; D001335:Vehicle Emissions; D020782:Matrix Metalloproteinases