C-reactive protein increases BBB permeability: implications for obesity and neuroinflammation

Cell Physiol Biochem. 2012;30(5):1109-19. doi: 10.1159/000343302. Epub 2012 Sep 27.

Abstract

Background/aims: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism*
  • C-Reactive Protein / metabolism*
  • Capillary Permeability*
  • Central Nervous System / metabolism*
  • Inflammation / metabolism*
  • Leptin / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Obesity / metabolism*

Substances

  • Leptin
  • C-Reactive Protein