Abstract:
Spinal cord injury (SCI) remains a worldwide challenge due to limited treatment strategies. Repetitive trans-spinal magnetic stimulation (rTSMS) is among the most cutting-edge treatments for SCI. However, the mechanism underlying rTSMS on functional recovery is still unclear. In this study, 8-week-old C57BL/6J female mice were used to design SCI models followed by treatment with monotherapy (1 Hz rTSMS or LY364947) or combination therapy (rTSMS + LY364947). Our results showed obvious functional recovery after monotherapies compared to untreated mice. Immunofluorescence results demonstrated that rTSMS and LY364947 modulate the lesion scar by decreasing fibrosis and GFAP and possess the effect on neural protection. In addition, rTSMS suppressed inflammation and the activation of TGFβ1/Smad2/3 signaling pathway, as evidenced by markedly reduced TGF-βRⅠ, Smad2/3, and p-Smad2/3 compared with untreated mice. Overall, it was confirmed that 1 Hz rTSMS promotes SCI recovery by suppressing the TGFβ1/Smad2/3 signaling, revealing a novel pathological mechanism of 1 Hz rTSMS intervention, and may provide potential targets for clinical treatment.
摘要:
脊髓损伤(SCI)仍然是一个全球性的挑战,由于有限的治疗策略。重复的经脊髓磁刺激(rTSMS)是SCI最尖端的治疗方法之一。然而,rTSMS对功能恢复的潜在机制尚不清楚.在这项研究中,8周龄C57BL/6J雌性小鼠用于设计SCI模型,随后用单一疗法(1HzrTSMS或LY364947)或组合疗法(rTSMS+LY364947)治疗。我们的结果显示,与未治疗的小鼠相比,单一疗法后的功能恢复明显。免疫荧光结果表明,rTSMS和LY364947通过减少纤维化和GFAP来调节病变瘢痕,并具有神经保护作用。此外,rTSMS抑制炎症和TGFβ1/Smad2/3信号通路的激活,TGF-βRⅠ显著降低,Smad2/3和p-Smad2/3与未处理的小鼠相比。总的来说,证实了1HzrTSMS通过抑制TGFβ1/Smad2/3信号促进SCI恢复,揭示了1HzrTSMS干预的新病理机制,并可能为临床治疗提供潜在的靶点。