Characterizing blood-brain barrier perturbations after exposure to human triglyceride-rich lipoprotein lipolysis products using MRI in a rat model.
Previous studies indicated hyperlipidemia may be a risk factor for Alzheimer's disease, but the contributions of postprandial triglyceride-rich lipoprotein (TGRL) are not known. In this study, changes in blood-brain barrier diffusional transport following exposure to human TGRL lipolysis products were studied using MRI in a rat model.



Male Sprague-Dawley rats (∼180-250 g) received an i.v. injection of lipoprotein lipase (LpL)-hydrolyzed TGRL (n = 8, plasma concentration ≈ 150 mg human TGRL/dL). Controls received i.v. injection of either saline (n = 6) or LpL only (n = 6). The (1) H longitudinal relaxation rate R1  = 1/T1 was measured over 18 min using a rapid-acquired refocus-echo (RARE) sequence after each of three injections of the contrast agent Gd-DTPA. Patlak plots were generated for each pixel yielding blood-to-brain transfer coefficients, Ki , chosen for best fit to impermeable, uni-directional influx or bi-directional flux models using the F-test.



Analysis from a 2-mm slice, 2-mm rostral to the bregma showed a 275% increase of mean Ki during the first 20 min after infusion of human TGRL lipolysis product that differed significantly compared with saline and LpL controls. This difference disappeared by 40 min mark.



These results suggest human TGRL lipolysis products can lead to a transient increase in rat BBB permeability. Magn Reson Med 76:1246-1251, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
School of Medicine, Division of Cardiovascular Medicine, University of California, Davis, California, USA.
Kit Fai
KF
Ng
School of Medicine, Department of Physiology and Membrane Biology, University of California, Davis, California, USA.
Steve
S
Anderson
School of Medicine, Division of Cardiovascular Medicine, University of California, Davis, California, USA.
Patrice
P
Mayo
School of Medicine, Division of Cardiovascular Medicine, University of California, Davis, California, USA.
Hnin Hnin
HH
Aung
NMR Facility and Biomedical Engineering Graduate Group, University of California, Davis, California, USA.
Jeffrey H
JH
Walton
School of Medicine, Division of Cardiovascular Medicine, University of California, Davis, California, USA. jcrutledge@ucdavis.edu.
John C
JC
Rutledge
D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology*; D007275:Injections, Intravenous; D008074:Lipoproteins / Q000008:administration & dosage*; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000008:administration & dosage*
D008074:Lipoproteins; D014280:Triglycerides; C030087:lipoprotein triglyceride
Gd-DTPA; blood-brain barrier; hyperlipidemia; permeability; triglyceride-rich lipoprotein