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.

Advances in fluorescent-image guided surgery

“…Recently developed fluorescently labeled peptides can specifically label degenerated nerve branches, which in the future could aid patients undergoing surgical nerve repair (140). Another fluorescent probe was capable of quantitatively evaluating traumatic brain injury (141). Though these probes have not yet been used in humans, combining them with existing imagining and surgical technology has the potential to increase the efficacy of future surgeries.…”

Zinc(II)-Dipicolylamine Coordination Complexes as Targeting and Chemotherapeutic Agents for Leishmania major

“…Another goal for future studies is to determine whether ZnDPA coordination complexes have activity against models of visceral Leishmaniasis. Fluorescent ZnDPA probes such as mSeek should be very helpful in determining systemic biodistribution, and we are encouraged by our previous work indicating that the biodistribution of ZnDPA probes is easily altered by rational structural modification (22)(23)(24)(25)(26)(27)(28). …”

“…1). Fluorescent ZnDPA probes are effective imaging agents for dead and dying mammalian cells (which expose anionic phosphatidylserine) in a range of cell culture systems and small animal models of disease (19)(20)(21)(22)(23)(24)(25)(26). ZnDPA probes also target the anionic surfaces of bacteria, and they have been used for imaging infection in animal models (27)(28)(29)(30)(31)(32)(33).…”

Electroconvulsive stimulation transiently enhances the permeability of the rat blood-brain barrier and induces astrocytic changes

“…Brains were imaged using a standard set of IVIS Lumina II filters (Perkin Elmer) (excitation filter, 465 nm; emission filter, Cy5.5; exposure time, 5 sec; bin, 2; f/stop, 9 2; field of view, 10 × 10 cm) [5,29]. Total Radiant Efficiency [Mp/sec]/[W/cm 2 ] (TRE; fluorescence strength) was measured for each brain.…”