Multicolor fluorescence imaging of traumatic brain injury in a cryolesion mouse model
Bryan A Smith1, Bang-Wen Xie, Ermond R van Beek
1Department of Chemistry and Biochemistry, 236 Nieuwland Science Hall, University of Notre Dame, Notre Dame, Indiana 46556, USA.
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.
Insights
A new fluorescent probe, PSS-794, effectively visualizes cell death in traumatic brain injury models. This molecular imaging method complements anatomical techniques, offering biochemical insights into brain injury progression.
Area of Science:
- Neuroscience
- Biomedical Imaging
- Molecular Probes
Background:
- Traumatic brain injury (TBI) involves initial damage, leading to secondary cell death and blood-brain barrier (BBB) disruption.
- Current clinical and preclinical TBI studies rely on anatomical imaging, necessitating novel molecular imaging for biochemical data.
- There is a need for advanced imaging techniques to better understand TBI pathophysiology.
Purpose of the Study:
- To assess the efficacy of a targeted near-infrared fluorescent probe, PSS-794, for detecting cell death in a TBI mouse model.
- To evaluate a deep-red tracer, Tracer-653, for monitoring BBB disruption.
- To enable multicolor imaging of both cell death and BBB permeability in a single animal.
Main Methods:
- A brain cryolesion mouse model was utilized to mimic aspects of TBI.
- Noninvasive whole-body fluorescence imaging was performed using PSS-794.
- Ex vivo imaging and histological analysis confirmed probe localization; Tracer-653 was used for BBB permeability assessment.
Main Results:
- PSS-794 successfully visualized the cryolesion in living animals, localizing to areas of cell death.
- Multicolor imaging revealed decreased cell death by day 3 post-injury.
- BBB integrity remained impaired at 3 and 7 days, with permeability significantly elevated at 7 days.
Conclusions:
- PSS-794 is a valuable tool for molecular imaging of cell death in TBI.
- Combined imaging of PSS-794 and Tracer-653 provides comprehensive biochemical information on TBI.
- The study highlights persistent BBB dysfunction following cryoinjury-induced TBI.
