Dynamic Analysis of the Blood-Brain Barrier Disruption in Experimental Stroke Using Time Domain in Vivo Fluorescence Imaging

The blood-brain barrier (BBB) disruption following cerebral ischemia can be exploited to deliver imaging agents and therapeutics into the brain. The aim of this study was (a) to establish novel in vivo optical imaging methods for longitudinal assessment of the BBB disruption and (b) to assess size s...

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Main Authors: Abedelnasser Abulrob, Eric Brunette, Jacqueline Slinn, Ewa Baumann, Danica Stanimirovic
Format: Article
Language:English
Published: SAGE Publishing 2008-11-01
Series:Molecular Imaging
Online Access:https://doi.org/10.2310/7290.2008.00025
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author Abedelnasser Abulrob
Eric Brunette
Jacqueline Slinn
Ewa Baumann
Danica Stanimirovic
author_facet Abedelnasser Abulrob
Eric Brunette
Jacqueline Slinn
Ewa Baumann
Danica Stanimirovic
author_sort Abedelnasser Abulrob
collection DOAJ
description The blood-brain barrier (BBB) disruption following cerebral ischemia can be exploited to deliver imaging agents and therapeutics into the brain. The aim of this study was (a) to establish novel in vivo optical imaging methods for longitudinal assessment of the BBB disruption and (b) to assess size selectivity and temporal patterns of the BBB disruption after a transient focal ischemia. The BBB permeability was assessed using in vivo time domain near-infrared optical imaging after contrast enhancement with either free Cy5.5 (1 kDa) or Cy5.5 conjugated with bovine serum albumin (BSA) (67 kDa) in mice subjected to either 60- or 20-minute transient middle cerebral artery occlusion (MCAO) and various times of reperfusion (up to 14 days). In vivo imaging observations were corroborated by ex vivo brain imaging and microscopic analyses of fluorescent tracer extravasation. The in vivo optical contrast enhancement with Cy5.5 was spatially larger than that observed with BSA-Cy5.5. Longitudinal studies after a transient 20-minute MCAO suggested a bilateral BBB disruption, more pronounced in the ipsilateral hemisphere, peaking at day 7 and resolving at day 14 after ischemia. The area differential between the BBB disruption for small and large molecules could potentially be useful as a surrogate imaging marker for assessing perinfarct tissues to which neuroprotective therapies of appropriate sizes could be delivered.
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spelling doaj-art-ecf9bc9fe99e45729316265c1df72ad62025-01-03T00:10:41ZengSAGE PublishingMolecular Imaging1536-01212008-11-01710.2310/7290.2008.0002510.2310_7290.2008.00025Dynamic Analysis of the Blood-Brain Barrier Disruption in Experimental Stroke Using Time Domain in Vivo Fluorescence ImagingAbedelnasser AbulrobEric BrunetteJacqueline SlinnEwa BaumannDanica StanimirovicThe blood-brain barrier (BBB) disruption following cerebral ischemia can be exploited to deliver imaging agents and therapeutics into the brain. The aim of this study was (a) to establish novel in vivo optical imaging methods for longitudinal assessment of the BBB disruption and (b) to assess size selectivity and temporal patterns of the BBB disruption after a transient focal ischemia. The BBB permeability was assessed using in vivo time domain near-infrared optical imaging after contrast enhancement with either free Cy5.5 (1 kDa) or Cy5.5 conjugated with bovine serum albumin (BSA) (67 kDa) in mice subjected to either 60- or 20-minute transient middle cerebral artery occlusion (MCAO) and various times of reperfusion (up to 14 days). In vivo imaging observations were corroborated by ex vivo brain imaging and microscopic analyses of fluorescent tracer extravasation. The in vivo optical contrast enhancement with Cy5.5 was spatially larger than that observed with BSA-Cy5.5. Longitudinal studies after a transient 20-minute MCAO suggested a bilateral BBB disruption, more pronounced in the ipsilateral hemisphere, peaking at day 7 and resolving at day 14 after ischemia. The area differential between the BBB disruption for small and large molecules could potentially be useful as a surrogate imaging marker for assessing perinfarct tissues to which neuroprotective therapies of appropriate sizes could be delivered.https://doi.org/10.2310/7290.2008.00025
spellingShingle Abedelnasser Abulrob
Eric Brunette
Jacqueline Slinn
Ewa Baumann
Danica Stanimirovic
Dynamic Analysis of the Blood-Brain Barrier Disruption in Experimental Stroke Using Time Domain in Vivo Fluorescence Imaging
Molecular Imaging
title Dynamic Analysis of the Blood-Brain Barrier Disruption in Experimental Stroke Using Time Domain in Vivo Fluorescence Imaging
title_full Dynamic Analysis of the Blood-Brain Barrier Disruption in Experimental Stroke Using Time Domain in Vivo Fluorescence Imaging
title_fullStr Dynamic Analysis of the Blood-Brain Barrier Disruption in Experimental Stroke Using Time Domain in Vivo Fluorescence Imaging
title_full_unstemmed Dynamic Analysis of the Blood-Brain Barrier Disruption in Experimental Stroke Using Time Domain in Vivo Fluorescence Imaging
title_short Dynamic Analysis of the Blood-Brain Barrier Disruption in Experimental Stroke Using Time Domain in Vivo Fluorescence Imaging
title_sort dynamic analysis of the blood brain barrier disruption in experimental stroke using time domain in vivo fluorescence imaging
url https://doi.org/10.2310/7290.2008.00025
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