Characterizing blood–brain barrier perturbations after exposure to human triglyceride-rich lipoprotein lipolysis products using MRI in a rat model

Kit Fai Ng, Steve Anderson, Patrice Mayo, Hnin Hnin Aung, Jeffrey H. Walton, John C Rutledge

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Purpose: 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. Methods: 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 1H 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. Results: 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. Conclusion: These results suggest human TGRL lipolysis products can lead to a transient increase in rat BBB permeability. Magn Reson Med 76:1246–1251, 2016.

Original languageEnglish (US)
Pages (from-to)1246-1251
Number of pages6
JournalMagnetic Resonance in Medicine
Volume76
Issue number4
DOIs
StatePublished - Oct 1 2016

Fingerprint

Lipolysis
Lipoproteins
Triglycerides
Lipoprotein Lipase
Injections
Gadolinium DTPA
Hyperlipidemias
Contrast Media
Sprague Dawley Rats
Permeability
Alzheimer Disease
Brain

Keywords

  • blood–brain barrier
  • Gd-DTPA
  • hyperlipidemia
  • permeability
  • triglyceride-rich lipoprotein

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Characterizing blood–brain barrier perturbations after exposure to human triglyceride-rich lipoprotein lipolysis products using MRI in a rat model. / Ng, Kit Fai; Anderson, Steve; Mayo, Patrice; Aung, Hnin Hnin; Walton, Jeffrey H.; Rutledge, John C.

In: Magnetic Resonance in Medicine, Vol. 76, No. 4, 01.10.2016, p. 1246-1251.

Research output: Contribution to journalArticle

Ng, Kit Fai ; Anderson, Steve ; Mayo, Patrice ; Aung, Hnin Hnin ; Walton, Jeffrey H. ; Rutledge, John C. / Characterizing blood–brain barrier perturbations after exposure to human triglyceride-rich lipoprotein lipolysis products using MRI in a rat model. In: Magnetic Resonance in Medicine. 2016 ; Vol. 76, No. 4. pp. 1246-1251.
@article{00f97ee6573f406f9d50672a67d7f88b,
title = "Characterizing blood–brain barrier perturbations after exposure to human triglyceride-rich lipoprotein lipolysis products using MRI in a rat model",
abstract = "Purpose: 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. Methods: 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 1H 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. Results: 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. Conclusion: These results suggest human TGRL lipolysis products can lead to a transient increase in rat BBB permeability. Magn Reson Med 76:1246–1251, 2016.",
keywords = "blood–brain barrier, Gd-DTPA, hyperlipidemia, permeability, triglyceride-rich lipoprotein",
author = "Ng, {Kit Fai} and Steve Anderson and Patrice Mayo and Aung, {Hnin Hnin} and Walton, {Jeffrey H.} and Rutledge, {John C}",
year = "2016",
month = "10",
day = "1",
doi = "10.1002/mrm.25985",
language = "English (US)",
volume = "76",
pages = "1246--1251",
journal = "Magnetic Resonance in Medicine",
issn = "0740-3194",
publisher = "John Wiley and Sons Inc.",
number = "4",

}

TY - JOUR

T1 - Characterizing blood–brain barrier perturbations after exposure to human triglyceride-rich lipoprotein lipolysis products using MRI in a rat model

AU - Ng, Kit Fai

AU - Anderson, Steve

AU - Mayo, Patrice

AU - Aung, Hnin Hnin

AU - Walton, Jeffrey H.

AU - Rutledge, John C

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Purpose: 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. Methods: 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 1H 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. Results: 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. Conclusion: These results suggest human TGRL lipolysis products can lead to a transient increase in rat BBB permeability. Magn Reson Med 76:1246–1251, 2016.

AB - Purpose: 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. Methods: 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 1H 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. Results: 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. Conclusion: These results suggest human TGRL lipolysis products can lead to a transient increase in rat BBB permeability. Magn Reson Med 76:1246–1251, 2016.

KW - blood–brain barrier

KW - Gd-DTPA

KW - hyperlipidemia

KW - permeability

KW - triglyceride-rich lipoprotein

UR - http://www.scopus.com/inward/record.url?scp=85027948488&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027948488&partnerID=8YFLogxK

U2 - 10.1002/mrm.25985

DO - 10.1002/mrm.25985

M3 - Article

C2 - 26485349

AN - SCOPUS:85027948488

VL - 76

SP - 1246

EP - 1251

JO - Magnetic Resonance in Medicine

JF - Magnetic Resonance in Medicine

SN - 0740-3194

IS - 4

ER -