title: In vivo optical imaging of ischemic blood-brain barrier disruption.
abstract: The blood-brain barrier (BBB) disruption following cerebral ischemia (stroke) contributes to the development of life-threatening brain edema. Recent studies suggested that the ischemic BBB disruption is not uniform throughout the affected brain region. The aim of this study was to establish in vivo optical imaging methods to assess the size selectivity and spatial distribution of the BBB disruption after a focal cerebral ischemia. The BBB permeability was assessed in mice subjected to a 60-min middle cerebral artery occlusion and 24 h of reperfusion using in vivo time domain near-infrared optical imaging after contrast enhancement with two tracers of different molecular size, Cy5.5 (1 kDa) and Cy5.5 conjugated with bovine serum albumin (BSA) (67 kDa). Volumetric reconstruction of contrast-enhanced brain areas in vivo and ex vivo indicated that the BSA-Cy5.5-enhancement is identical to the volume of infarct determined by TTC staining, whereas the volume of enhancement with Cy5.5 was 40% greater. The volume differential between areas of BBB disruption for small and large-size molecules could be useful for determining the size of peri-infarct tissues (penumbra) that can respond to neuroprotective therapies.
authors.affiliation: Institute for Biological Sciences, National Research Council of Canada, Ottawa, ON, Canada. Abedelnasser.Abulrob@nrc.gc.ca
authors.forename: Abedelnasser
authors.initials: A
authors.lastname: Abulrob
authors.forename: Eric
authors.initials: E
authors.lastname: Brunette
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Slinn
authors.forename: Ewa
authors.initials: E
authors.lastname: Baumann
authors.forename: Danica
authors.initials: D
authors.lastname: Stanimirovic
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002232:Carbocyanines / Q000032:analysis / Q000378:metabolism; D002417:Cattle; D054893:Cone-Beam Computed Tomography / Q000379:methods*; D003287:Contrast Media / Q000032:analysis / Q000378:metabolism*; D004195:Disease Models, Animal; D005453:Fluorescence; D006651:Histocytochemistry; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008867:Microtomy; D057054:Molecular Imaging / Q000379:methods*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D012709:Serum Albumin / Q000032:analysis / Q000378:metabolism; D013778:Tetrazolium Salts / Q000032:analysis
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D003287:Contrast Media; D012709:Serum Albumin; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium