Similar to the Translational Therapeutics Core, the Optimizing Ferret TBI Experiment is a standardized, complex TBI paradigm in ferrets. As with the Translational Therapeutics Core, this model replicates TBIs experienced by Service Members by combining blast exposure and rotational impact with a variety of environmental stressors. The Optimizing Ferret TBI Experiment also incorporates novel pre-and post-injury behavioral tests to evaluate changes in mood, headache, and sleep. Soon, this model will test the efficacy of candidate treatments. Mimicking clinical trial standards, these experiments will be randomized, blinded, and placebo controlled with prespecified primary and secondary outcome measures at 6 months. Effective treatments will be shared with the Clinical Trials Unit and incorporated in the design of early phase clinical trials.
Like humans, ferrets have gyrencephalic brains with a substantial amount of white matter, and a ventral position of the hippocampus. Depending on the injury, ferrets display post-injurious symptoms analogous to humans, such as significant changes in speed, motor abilities, and memory function. Blast injury models show patterns of gliosis comparable to those observed in humans. These models show reliable changes in the pattern of expression of tau isoforms 3R and 4R, as well as increases in levels of phosphorylated tau. The changes in the 3R and 4R isoforms are highly relevant, because several human pathologies show substantial alterations in the expression ratio of these isoforms, which have been difficult to demonstrate in rodents. These similarities increase the potential of the ferret model to translate promising interventions into future successful clinical trials.