Similar to the Translational Therapeutics Core, our Optimizing Ferret TBI Experiment is a standardized, complex traumatic brain injury (TBI) paradigm in ferrets. This model combines repeated blast exposures with rotational impact and a variety of environmental stressors to replicate TBIs experienced by service members.
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. Integrating 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 our 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 that are comparable to humans, such as significant changes in speed, motor abilities, and memory function.
Blast injury models also show patterns of gliosis that are 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.