Traumatic brain injury (TBI) is one of the foremost causes of disability and mortality globally. While the scientific and medical emphasis is to save lives and avoid disability during acute period of injury, a severe health problem can manifest years after injury. For instance, TBI increases the risk of cognitive impairment in the elderly. Remote TBI history was reported to be a cause of the accelerated clinical trajectory of Alzheimer’s disease-related dementia (ADRD) resulting in earlier onset of cognitive impairment and increased AD-associated pathological markers like greater amyloid deposition and cortical thinning. It is not well understood whether a single TBI event may increase the risk of dementia. Moreover, the cellular signaling pathways remain elusive for the chronic effects of TBI on cognition. We have hypothesized that a single TBI induces sustained neuroinflammation and disrupts cellular communication in a way that results later in ADRD pathology. To test this, we induced TBI in young adult CD1 mice and assessed the behavioral outcomes after 11 months followed by pathological, histological, transcriptomic, and MRI assessment. On MRI scans, these mice showed significant loss of tissue, reduced CBF, and higher white matter injury compared to sham mice. We found these brains showed progressive atrophy, markers of ADRD, sustained astrogliosis, loss of neuronal plasticity, and growth factors even after 1-year post-TBI. Because of progressive neurodegeneration, these mice had motor deficits, showed cognitive impairments, and wandered randomly in open field. We, therefore, conclude that progressive pathology after adulthood TBI leads to neurodegenerative conditions such as ADRD and impairs neuronal functions.

创伤性脑损伤（TBI）是全球残疾和死亡的最主要原因之一。虽然科学和医学的重点是在受伤急性期挽救生命并避免残疾，但严重的健康问题可能会在受伤数年后显现出来。例如，TBI 会增加老年人认知障碍的风险。据报道，远期 TBI 病史是导致阿尔茨海默病相关痴呆 (ADRD) 临床轨迹加速的一个原因，导致认知障碍更早发病，并增加 AD 相关病理标志物，如更多的淀粉样蛋白沉积和皮质变薄。目前尚不清楚一次 TBI 事件是否会增加患痴呆症的风险。此外，TBI 对认知的慢性影响的细胞信号传导途径仍然难以捉摸。我们假设，单一的 TBI 会诱发持续的神经炎症并扰乱细胞通讯，从而导致 ADRD 病理。为了测试这一点，我们在年轻的成年 CD1 小鼠中诱导 TBI，并评估 11 个月后的行为结果，然后进行病理、组织学、转录组和 MRI 评估。在 MRI 扫描中，与假手术小鼠相比，这些小鼠表现出明显的组织损失、CBF 减少和更高的白质损伤。我们发现，即使在 TBI 后 1 年后，这些大脑仍表现出进行性萎缩、ADRD 标志物、持续性星形胶质细胞增生、神经元可塑性和生长因子丧失。由于进行性神经退行性变，这些小鼠出现运动缺陷，表现出认知障碍，并且在旷野中随意徘徊。因此，我们得出结论，成年 TBI 后的进行性病理会导致 ADRD 等神经退行性疾病，并损害神经元功能。