Abstract: Traumatic spinal cord injury (SCI) is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide. Advances in assistive technology, rehabilitative interventions, and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients, with some people even living well into their seventh or eighth decade. These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging. Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life, along with a higher risk of comorbidities and complications. Although extensive effort has been spent on promoting the recovery of locomotor and sensory functions, little research has focused on pathophysiological changes in the brain. One of the long-term consequences of SCI is neuropsychological impairment, which includes deficits in memory, executive functions, attention span, processing speed, and learning abilities. Clinical studies show that SCI patients are more likely to be diagnosed with depression, anxiety, dementia, and other neurological disorders of the brain (Craig et al., 2017; Sachdeva et al., 2018; Distel et al., 2020). In fact, one study showed that SCI patients are 13 times more likely to show cognitive and emotional deficits (Craig et al., 2017). These reported cognitive impairments and mood disorders will not only compromise SCI patients’ quality of life and prognosis but also have deleterious effects on rehabilitation and recovery. However, despite these serious implications, few studies have focused on the underlying mechanisms of brain dysfunctions following SCI.