title: Multicolor fluorescence imaging of traumatic brain injury in a cryolesion mouse model.
abstract: Traumatic brain injury is characterized by initial tissue damage, which then can lead to secondary processes such as cell death and blood-brain-barrier disruption. Clinical and preclinical studies of traumatic brain injury typically employ anatomical imaging techniques and there is a need for new molecular imaging methods that provide complementary biochemical information. Here, we assess the ability of a targeted, near-infrared fluorescent probe, named PSS-794, to detect cell death in a brain cryolesion mouse model that replicates certain features of traumatic brain injury. In short, the model involves brief contact of a cold rod to the head of a living, anesthetized mouse. Using noninvasive whole-body fluorescence imaging, PSS-794 permitted visualization of the cryolesion in the living animal. Ex vivo imaging and histological analysis confirmed PSS-794 localization to site of brain cell death. The nontargeted, deep-red Tracer-653 was validated as a tracer dye for monitoring blood-brain-barrier disruption, and a binary mixture of PSS-794 and Tracer-653 was employed for multicolor imaging of cell death and blood-brain-barrier permeability in a single animal. The imaging data indicates that at 3 days after brain cryoinjury the amount of cell death had decreased significantly, but the integrity of the blood-brain-barrier was still impaired; at 7 days, the blood-brain-barrier was still three times more permeable than before cryoinjury.
authors.affiliation: Department of Chemistry and Biochemistry, 236 Nieuwland Science Hall, University of Notre Dame, Notre Dame, Indiana 46556, USA.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Smith
authors.forename: Bang-Wen
authors.initials: BW
authors.lastname: Xie
authors.forename: Ermond R
authors.initials: ER
authors.lastname: van Beek
authors.forename: Ivo
authors.initials: I
authors.lastname: Que
authors.forename: Vicky
authors.initials: V
authors.lastname: Blankevoort
authors.forename: Shuzhang
authors.initials: S
authors.lastname: Xiao
authors.forename: Erin L
authors.initials: EL
authors.lastname: Cole
authors.forename: Mathias
authors.initials: M
authors.lastname: Hoehn
authors.forename: Eric L
authors.initials: EL
authors.lastname: Kaijzel
authors.forename: Clemens W G M
authors.initials: CW
authors.lastname: Löwik
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Smith
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000175:diagnosis* / Q000378:metabolism*; D003452:Cryosurgery / Q000009:adverse effects; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D008819:Mice, Nude; D061848:Optical Imaging / Q000379:methods*