Traumatic brain injury (TBI) is defined as an injury to the head that disrupts normal brain function. TBI has been described as a disease process that can lead to an increased risk for developing chronic neurodegenerative diseases, like frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). A pathological hallmark of FTLD and a hallmark of ALS is the nuclear mislocalization of TAR DNA Binding Protein 43 (TDP-43). This project aims to explore neurodegenerative effects of TBI on cortical lesion area using immunohistochemical markers of TDP-43 proteinopathies. We analyzed the total percent of NEUN positive cells displaying TDP-43 nuclear mislocalization. We found that the percent of NEUN positive cells displaying TDP-43 nuclear mislocalization was significantly higher in cortical tissue following TBI when compared to the age-matched control brains. The cortical lesion area was analyzed for each injured brain sample, with respect to days post-injury (DPI), and it was found that there were no statistically significant differences between cortical lesion areas across time points. The percent of NEUN positive cells displaying TDP-43 nuclear mislocalization was analyzed for each cortical tissue sample, with respect to cortical lesion area, and it was found that there were no statistically significant differences between the percent of NEUN positive cells displaying TDP-43 nuclear mislocalization, with respect to cortical lesion area. In conclusion, we found no correlation between the percent of cortical NEUN positive cells displaying TDP-43 nuclear mislocalization with respect to the size of the cortical lesion area.