@article{oai:repo.qst.go.jp:00046359,
 author = {Tomizawa, Atsuyuki and Ishii, Itsuko and Zhelev, Zhivko and Aoki, Ichio and Shibata, Sayaka and Bakalova-Zheleva, Rumiana and Kitada, Mitsukazu and 石井 伊都子 and Ｚｈｅｌｅｖ Ｚｈｉｖｋｏ and 青木 伊知男 and 柴田 さやか and バカロバ ルミアナ},
 issue = {12},
 journal = {Biochimica et Biophysica Acta. General Subjects},
 month = {Jun},
 note = {BACKGROUND: Gd-DTPA-enhanced magnetic resonance imaging (MRI) is a conventional method for non-invasive investigation of blood-brain-barrier (BBB) permeability in animal models. It allows the visualization of serious injury to the BBB. We developed a novel approach for detecting very small disruptions in BBB permeability induced by dietary cholesterol by using carbamoyl-PROXYL (CMP) as an MRI contrast probe.
\nMETHODS: Mice were separated into two groups: normal diet (ND-mice) and high cholesterol diet (CD-mice). MRI-signal dynamics, plasma cholesterol, matrix metalloproteinase (MMP-9, MMP-2), and the white blood cell profile were analyzed. For the MRI analysis, two regions-of-interest (ROI) were selected: brain (ROI-1) and surrounding area (ROI-2).
\nRESULTS: In the ROI-2 of ND-mice, CMP- or Gd-enhanced MRI-signal followed typical kinetics with a half-life of signal decay (t(1/2)) ~8 or ~15min, respectively. In CD-mice, the MRI-signal increased continuously without decay. In the ROI-1 of ND- and CD-mice, MRI-signal enhancement was not detected by Gd-DTPA. In the ROI-1 of ND-mice, CMP-induced MRI-signal enhancement was negligible, while in CD-mice, it was significant (t(1/2)>15min). Hypercholesterolemia increased the plasma levels of MMP-9 and neutrophils.
\nCONCLUSIONS: Hypercholesterolemia increases vascular permeability, which is mediated by MMP-9 and neutrophils.
\nGENERAL SIGNIFICANCE: Even very small disruptions in brain vascular permeability could be detected by CMP-enhanced MRI but not by Gd-DTPA-enhanced MRI.},
 pages = {1309--1316},
 title = {Carbamoyl-PROXYL-enhanced MRI detects very small disruptions in brain vascular permeability induced by dietary cholesterol.},
 volume = {1810},
 year = {2011}
}