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MRI detection of early endothelial activation in brain inflammation

Record type: Article

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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Citation

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), pp. 248-252. (doi:10.1002/mrm.10723).

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: 17 Jul 2017 14:32

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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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