| First Author | Hsuchou H | Year | 2012 |
| Journal | Cell Physiol Biochem | Volume | 30 |
| Issue | 5 | Pages | 1109-19 |
| PubMed ID | 23018453 | Mgi Jnum | J:322432 |
| Mgi Id | MGI:6708227 | Doi | 10.1159/000343302 |
| Citation | Hsuchou H, et al. (2012) C-reactive protein increases BBB permeability: implications for obesity and neuroinflammation. Cell Physiol Biochem 30(5):1109-19 |
| abstractText | 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. |
