A traumatic brain injury (TBI) occurs when the skull is subjected to mechanical force, resulting in long-lasting alterations to the central nervous system (CNS). TBI often leads to neurodegenerative consequences, such as proteinopathies, including TAR DNA binding protein 43 (TDP-43), and activation of the glial cells. Recent research indicated that TBI induces changes in CNS regions further from the initial site of injury, such as hippocampus, thalamus and cerebellum. This study aimed to examine the pathophysiological alterations, including those related to TDP-43 proteinopathy, in the spinal cord of mice, 14 days following a single moderate TBI or last repetitive mild TBIs. The lateral fluid percussion injury method has been used to induce a single moderate brain trauma and weight-drop method has been used to induce the repetitive mild TBIs. Sham injured animals were used as a control group. Histological evaluation of the mice spinal cord sections did not reveal morphological changes following neither single moderate nor repetitive brain injuries. Glial response and cytoplasmatic mislocalization of TDP-43 were present after both single moderate and repetitive TBIs. Subtle pathological changes following different types of TBIs, detected at the remote sites from the impact, increase the interest for more thorough understanding of secondary injury triggering factors, like TDP-43 pathology. It seems promising that new therapeutic approaches for primary neurodegenerative conditions, like amyotrophic lateral sclerosis or Alzheimer’s disease, but also injuries with neurodegeneration as a secondary event, like TBI, can be established by targeting cellular processes that contribute to the pathological processes of TDP-43.