Dynamic analysis of the blood-brain barrier disruption in experimental stroke using time domain in vivo fluorescence imaging

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TypeArticle
Journal titleMol.Imaging
Volume7
Issue6
Pages248262; # of pages: 15
Subjectanalysis; Animals; Blood-Brain Barrier; Brain; Canada; Cell Membrane Permeability; Cerebral Arteries; Coronary Circulation; Disease Models,Animal; DOMAIN; ENHANCEMENT; Ischemia; Kinetics; Male; method; Methods; Mice; Microscopy,Fluorescence; Middle Cerebral Artery; MOLECULE; pathology; Reperfusion; Serum; Stroke; therapy
AbstractThe 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
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedNo
NRC numberABULROB2008
NPARC number9389177
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Record identifier581f3dfa-0c69-4886-8e57-7b2a9925041f
Record created2009-07-10
Record modified2016-05-09
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