title: C-reactive protein increases BBB permeability: implications for obesity and neuroinflammation.
abstract: OBJECTIVE
  Acute phase C-reactive protein (CRP), elevated in obesity and inflammation, is a major binding protein for leptin. It is thought that CRP contributes to leptin resistance by preventing leptin from crossing the blood-brain barrier (BBB). Here we determined how CRP interacts with the BBB and whether it deters leptin from reaching CNS targets.
  
  
  METHODS
  BBB permeability, compartmental distribution, tracer stability, and expression of tight junction protein and inflammatory marker were determined.
  
  
  RESULTS
  CRP was stable in blood, but did not permeate the BBB in trace amounts. However, it increased paracellular permeability at a higher dose. Agouti viable (A(vy)) mice with adult-onset obesity show higher CRP entry into the brain. CRP did not permeate hCMEC/D3 cells nor change zona occludin-1 or cyclooxygenase-2 expression. An intermediate dose of CRP had no effect on leptin transport across the BBB after co-treatment. Thus, acute interactions between CRP and leptin at the BBB level were negligible and did not explain the leptin resistance seen in obesity.
  
  
  CONCLUSIONS
  The interactions of CRP and the BBB are a two-phase process, with increased paracellular permeability at a high dose that enables its entry into the CNS and serves to induce reactive gliosis and impair CNS function.
authors.affiliation: Blood-Brain Barrier Group, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
authors.forename: Hung
authors.initials: H
authors.lastname: Hsuchou
authors.forename: Abba J
authors.initials: AJ
authors.lastname: Kastin
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Mishra
authors.forename: Weihong
authors.initials: W
authors.lastname: Pan
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism*; D002199:Capillary Permeability; D002490:Central Nervous System / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*
chemical_list: D020738:Leptin; D002097:C-Reactive Protein