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MRI detection of early endothelial activation in brain inflammation

MRI detection of early endothelial activation in brain inflammation
MRI detection of early endothelial activation in brain inflammation
MRI is an increasingly important clinical tool, but it is clear that conventional imaging fails to identify the full extent of lesion load in certain conditions, such as multiple sclerosis. The aim of this study was to determine whether a novel contrast agent (Gd-DTPA-B(sLeX)A, which contains an sLeX mimetic moiety that enables it to bind to the adhesion molecule E-selectin) can be used to identify endothelial activation in the brain. Microinjection of the proinflammatory cytokines IL-1or TNF- into the striatum of Wistar rats rapidly induces focal adhesion molecule expression on the endothelium in the absence of MRI-visible changes. This phenomenon was used to investigate the potential of Gd-DTPA-B(sLeX)A to reveal MRI-invisible brain pathology. T1-weighted serial images were acquired in anesthetized animals before and after administration of Gd-DTPA-B(sLeX)A, 3-4 hr after cytokine was injected intracerebrally. Both TNF- and IL-1 up-regulated E-selectin on the brain endothelium, which correlated with increased signal intensity observed after administration of the novel contrast agent. No enhancement was visible with the nonselective contrast agent Gd-DTPA-BMA, indicating that there was no leakage of the agent across the blood-brain barrier (BBB) or nonselective binding to the endothelium. These data demonstrate the potential of such contrast agents for the early detection of brain injury and inflammation.
magnetic resonance, brain, inflammation, E-selectin, rat
0740-3194
248-252
Sibson, Nicola R.
408b5626-2da8-4fc8-9fb5-bbe52a7b8aaf
Blamire, Andrew M.
9e32053d-5a8f-4358-b1c1-eb16e5d67b8d
Bernades-Silva, Martine
544038fe-9100-4432-9f35-d003e4d03234
Laurent, Sophie
c8327d14-a5a5-4449-86d3-3910a1192426
Boutry, Sébastien
15c68d1d-1f76-47d5-8957-4d77af72bb9a
Muller, Robert N.
d571d382-ce85-413e-9327-dd82dca07df9
Styles, Peter
2a4bcc97-b4cb-45c2-807c-7f4e54b916d2
Anthony, Daniel C.
928249fa-dcf4-4088-b95b-ce14c719164d
Sibson, Nicola R.
408b5626-2da8-4fc8-9fb5-bbe52a7b8aaf
Blamire, Andrew M.
9e32053d-5a8f-4358-b1c1-eb16e5d67b8d
Bernades-Silva, Martine
544038fe-9100-4432-9f35-d003e4d03234
Laurent, Sophie
c8327d14-a5a5-4449-86d3-3910a1192426
Boutry, Sébastien
15c68d1d-1f76-47d5-8957-4d77af72bb9a
Muller, Robert N.
d571d382-ce85-413e-9327-dd82dca07df9
Styles, Peter
2a4bcc97-b4cb-45c2-807c-7f4e54b916d2
Anthony, Daniel C.
928249fa-dcf4-4088-b95b-ce14c719164d

Sibson, Nicola R., Blamire, Andrew M., Bernades-Silva, Martine, Laurent, Sophie, Boutry, Sébastien, Muller, Robert N., Styles, Peter and Anthony, Daniel C. (2004) MRI detection of early endothelial activation in brain inflammation. Magnetic Resonance in Medicine, 51 (2), 248-252. (doi:10.1002/mrm.10723).

Record type: Article

Abstract

MRI is an increasingly important clinical tool, but it is clear that conventional imaging fails to identify the full extent of lesion load in certain conditions, such as multiple sclerosis. The aim of this study was to determine whether a novel contrast agent (Gd-DTPA-B(sLeX)A, which contains an sLeX mimetic moiety that enables it to bind to the adhesion molecule E-selectin) can be used to identify endothelial activation in the brain. Microinjection of the proinflammatory cytokines IL-1or TNF- into the striatum of Wistar rats rapidly induces focal adhesion molecule expression on the endothelium in the absence of MRI-visible changes. This phenomenon was used to investigate the potential of Gd-DTPA-B(sLeX)A to reveal MRI-invisible brain pathology. T1-weighted serial images were acquired in anesthetized animals before and after administration of Gd-DTPA-B(sLeX)A, 3-4 hr after cytokine was injected intracerebrally. Both TNF- and IL-1 up-regulated E-selectin on the brain endothelium, which correlated with increased signal intensity observed after administration of the novel contrast agent. No enhancement was visible with the nonselective contrast agent Gd-DTPA-BMA, indicating that there was no leakage of the agent across the blood-brain barrier (BBB) or nonselective binding to the endothelium. These data demonstrate the potential of such contrast agents for the early detection of brain injury and inflammation.

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More information

Published date: 2004
Keywords: magnetic resonance, brain, inflammation, E-selectin, rat

Identifiers

Local EPrints ID: 55562
URI: http://eprints.soton.ac.uk/id/eprint/55562
ISSN: 0740-3194
PURE UUID: bdedb021-0696-4081-b084-4b97205bee70

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Date deposited: 01 Aug 2008
Last modified: 08 Jan 2022 19:04

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Contributors

Author: Nicola R. Sibson
Author: Andrew M. Blamire
Author: Martine Bernades-Silva
Author: Sophie Laurent
Author: Sébastien Boutry
Author: Robert N. Muller
Author: Peter Styles
Author: Daniel C. Anthony

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