Department of Physical Medicine and Rehabilitation, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
Department of Physical Medicine and Rehabilitation, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China; Department of Intelligent Rehabilitation International (cross-strait) Alliance of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
Neurochem Int. 2021 Feb;143:104945. doi: 10.1016/j.neuint.2020.104945. Epub 2020 Dec 24.
Following spinal cord injury (SCI), destruction of the blood-spinal cord barrier (BSCB) leads to increased microvascular permeability and tissue oedema. The BSCB, formed by a dense network of tight junctions (TJs) and adhesion junctions (AJs) is considered a therapeutic target. Most studies have focused on the effect of drug therapy on the neurovascular system after SCI, ignoring the protection and functional recovery of the vascular system by exercise training. Previously, we indicated that water treadmill training (TT) has a protective effect on the BSCB after SCI, but the specific molecular mechanism of the effect of TT on BSCB is still not clear. In this study, we used a specific inhibitor of TrkB (ANA-12) to explore whether the BDNF/TrkB-CREB signalling pathway is involved in TT-mediated BSCB protection after SCI. A New York University (NYU) impactor was used to establish the SCI model. Rats in the SI (Sham + ANA-12), IM (SCI + ANA-12) and ITM (SCI + TT + ANA-12) groups were injected with ANA-12 (0.5 mg/kg) daily, and rats in TM (SCI + TT) and ITM (SCI + TT + ANA-12) groups were treated with water TT for 7 or 14 d. The degree of neurological deficit, water content, BSCB permeability, protein expression and ultrastructure of vascular endothelial cells were assessed by the Basso-Beattie-Bresnahan (BBB) motor rating scale, Evans blue (EB), Western blot (WB) experiments, immunofluorescence and transmission electron microscopy (TEM). Our results suggest that TT upregulates the BDNF/TrkB-CREB signalling pathway following SCI. The BDNF/TrkB-CREB signalling pathway is involved in the protection of the BSCB. Application of the inhibitor blocked the protective effect of TT on the BSCB. We concluded that TT ameliorated SCI-induced BSCB impairment by upregulating the BDNF/TrkB-CREB signalling pathways.
脊髓损伤（SCI）后，血脊髓屏障（BSCB）的破坏导致微血管通透性增加和组织水肿。BSCB 由紧密连接（TJ）和黏附连接（AJ）组成的致密网络形成，被认为是治疗靶点。大多数研究都集中在 SCI 后药物治疗对神经血管系统的影响上，而忽略了运动训练对血管系统的保护和功能恢复。之前，我们表明水跑台训练（TT）对 SCI 后 BSCB 具有保护作用，但 TT 对 BSCB 影响的具体分子机制仍不清楚。在这项研究中，我们使用了一种特定的 TrkB 抑制剂（ANA-12）来探讨 BDNF/TrkB-CREB 信号通路是否参与 TT 介导的 SCI 后 BSCB 保护作用。使用纽约大学（NYU）撞击器建立 SCI 模型。SI（假手术+ANA-12）、IM（SCI+ANA-12）和 ITM（SCI+TT+ANA-12）组大鼠每天注射 ANA-12（0.5mg/kg），TM（SCI+TT）和 ITM（SCI+TT+ANA-12）组大鼠进行水 TT 治疗 7 或 14d。通过 Basso-Beattie-Bresnahan（BBB）运动评分量表、伊文思蓝（EB）、Western blot（WB）实验、免疫荧光和透射电镜（TEM）评估神经功能缺损程度、水含量、BSCB 通透性、血管内皮细胞蛋白表达和超微结构。结果表明，TT 上调 SCI 后 BDNF/TrkB-CREB 信号通路。BDNF/TrkB-CREB 信号通路参与 BSCB 的保护作用。抑制剂的应用阻断了 TT 对 BSCB 的保护作用。我们得出结论，TT 通过上调 BDNF/TrkB-CREB 信号通路改善 SCI 引起的 BSCB 损伤。
