*3.3. Repetitive mTBI Did Not Affect Barnes Maze Task in Wild-Type and TDP-43G348C Mice at 6 Months Following Repetitive mTBI*

In the current research, we evaluated the effects of repetitive mTBI on the possibility of successful performance in the Barnes maze task. The Barnes maze task is usually used as a spatial learning/memory test in rodents taking advantage of their innate behavior to run away from brightly illuminated to dark areas [80]; however, in our study, it was applied primarily to test the functional status of the visual system following repeated head traumas. No differences in the time to escape to the target hole or in the time spent in the target quadrant were observed between the experimental groups, suggesting that neuronal damage, axonal damage, and neuroinflammation detected in the OT at 6 months after the last head trauma, as well as genetic TDP-43 background, did not influence the performance in the Barnes maze task. In addition, the Barnes maze task, as a cognitive test, was performed in some other studies in rodents of different ages and genotypes in which various repetitive mTBI methods, severity of the injuries, protocols, tested parameters, and posttraumatic periods were used, which is the reason why the obtained results are not consistent and hardly reciprocally comparable [33,59,69,81–83]. Previously, it was shown that TDP-43G348C animals exhibited a significant reduction in the time spent in the target quadrant and increased primary errors in the Barnes maze test as compared with age-matched wild-type mice at 10 months of age [28]. In our study, all mice, including these transgenic traumatized and control animals, performed the task equally at approximately 8.5 months of age. Further studies are needed in order to explore age-dependent behavior of TDP-43G348C mice in the Barnes maze task.

In summary, current study results suggest that repetitive mTBI induced damage of the OT, but did not affect the nuclei that transmit information from the retinal ganglion cells to the visual cortex, as well as mouse behavior that includes preserved vision, at 6 months after the last head impact. In addition, genetic TDP-43 background did not influence the assessed neuropathology and behavior in experimental animals. This study could improve our knowledge and understanding of chronic neuropathological changes in the visual system following repetitive mTBI and the role of TDP-43 proteinopathy in these processes.

## **4. Materials and Methods**
