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Biomechanics

Biomechanics - Poster Session C

Poster E7 - Investigation of Behavioral and Cognitive Alterations using a Ferret Model of Traumatic Brain Injury

Friday, October 25, 2024
10:00 AM - 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Traumatic Brain Injury (TBI), with millions of occurrences yearly [1], represents a significant public health concern in the USA. Depends on the severity, TBI can lead to short- and long-term cognitive and emotional deficits, memory impairment, and motor function disabilities. This highlights the need for further research to find a correlation between severity of TBI and potential consequences. The main driving cause of TBI is recognized to be the brain tissue deformations caused by rapid head rotations. In this study, we utilized a ferret CHIMERA model that has shown its utility in modeling rapid rotational head injuries with outcomes that closely mirror human TBI. Ferrets were chosen for their brain structure and social capability that have similarities to humans. Our objective was to analyze the behavioral following TBI in ferrets over a course of a week.

Materials and

Methods:  Animals were divided into repeated TBI (n=9) and sham (n=8) groups. The TBI group received one high-severity impact (~16 m/s), followed by three mild impacts (~10 m/s) at 10-minute intervals. sham group underwent the same procedure without the actual impact. Behavioral assessments were performed at baseline and at 1-day, 3-days, and 7-days post-TBI or post-experiment in sham group (1DPI, 3DPI, 7DPI). For the open field test, the ferrets were moved from their cages to a 1m x 1m open field setup and observed for 10 minutes using an overhead camera system. For the novel object recognition test, ferrets were placed in a cage with two objects for 10 minutes. After a 1-hour interval, they were returned to the cage with one known object replaced by a novel object. Ferrets' movements were analyzed using AnyMaze software, and changes in behavioral parameters, including average speed, total distance traveled, and retention index (RI= (total time spent with novel object)/(total time spent with both object)*100), were calculated. Samples of ferret’s movement in the open field setup provided in Figure1. The behavioral tests aimed to monitor the progression and potential recovery of behavioral and psychological changes following TBI.

Results, Conclusions, and Discussions: Statistical analysis revealed significant differences (Wilcoxon Signed-Ranks, p-value < 0.05) between 1DPI and 7DPI for both groups, possibly due to the effect of long anesthesia at the experiment day, and between 3DPI and 7DPI for just the TBI group. Additionally, significant differences (Mann-Whitney, p-value < 0.05) were found in anxiety-associated parameters—average speed and total distance traveled—between sham and TBI groups especially at 7DPI , when the effects of medication and anesthesia had disappeared. This indicates a delayed development of anxiety like behaviors [2]. Analyzing the results from novel object test, only the TBI group exhibited a RI lower than %50, indicating memory disturbance due to the injury [3], at 1DPI and 7DPI. Comparing the groups at different timepoints only showed significant difference (Mann-Whitney, p-value < 0.05) at 7DPI. This study highlights the significant behavioral deficits caused by TBI, with an elevation in anxiety-like behaviors and memory disturbance. These results emphasize the need for further research on the correlation between TBI severity and behavioral consequences, aiming to better understand the underlying mechanisms.

Acknowledgements (Optional):  UTSA-SwRI CONNECT program and NIH ESTEEMED 2R25EB027605-06
References - [1] Taylor et al. MMWR Surveill Summ 2017;66(No. SS-9):1–16. DOI: dx.doi.org/10.15585/mmwr.ss6609a1
[2] Bagherian et al. Journal of Neurotrauma.A-1-A-121. doi:10.1089/neu.2024.41112
[3] Schwerin et al. Journal of neuroscience methods. 2017; 285:82-96.