在脊髓损伤后，脑脊液中总tau和高度磷酸化tau的浓度增加，两者水平与损伤严重程度相关。抑制tau被认为是许多中枢神经系统疾病的有效治疗方法，包括颅脑损伤和阿尔茨海默病。然而，它是否可以在脊髓损伤的治疗中发挥作用仍不清楚。在这项研究中，通过注射编码抑制tau表达的tau siRNA的慢病毒，探究了tau抑制的治疗效果，以大鼠切断脊髓损伤模型为对象。我们发现，脊髓损伤后tau抑制降低了炎症介质的水平，包括肿瘤坏死因子-α、白细胞介素-6和白细胞介素-1β。它还导致激活的小胶质细胞极化从M1促炎症表型向M2抗炎症表型转变，并减少急性期的反应性氧化物。此外，残余神经细胞的存活率和神经元及轴突再生也显著增强，促进了模型大鼠的运动恢复。总体而言，我们的发现支持tau抑制可以减轻神经炎症、缓解氧化压力、保护残余细胞、促进神经发生并改善脊髓损伤后的功能恢复的结论，因此表明tau可能是脊髓损伤治疗的良好分子靶点。

After spinal cord injury, the concentrations of total and hyperphosphorylated tau in cerebrospinal fluid increase, and levels of both correlate with injury severity. Tau inhibition is considered effective therapy for many central nervous system diseases, including traumatic brain injury and Alzheimer's disease. However, whether it can play a role in the treatment of spinal cord injury remains unclear. In this study, the therapeutic effects of tau inhibition were investigated in a rat model of transection spinal cord injury by injecting the rats with a lentivirus encoding tau siRNA that inhibits tau expression. We found that tau inhibition after spinal cord injury down-regulated the levels of inflammatory mediators, including tumor necrosis factor-α, interleukin-6 and interleukin-1β. It also led to a shift of activated microglial polarization from the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype, and reduced the amount of reactive oxygen species in the acute phase. Furthermore, the survival of residual neural cells around the injury epicenter, and neuronal and axonal regeneration were also markedly enhanced, which promoted locomotor recovery in the model rats. Collectively, our findings support the conclusion that tau inhibition can attenuate neuroinflammation, alleviate oxidative stress, protect residual cells, facilitate neurogenesis, and improve the functional recovery after spinal cord injury, and thus suggest that tau could be a good molecular target for spinal cord injury therapy.