阻断脑源性神经营养因子-酪氨酸激酶受体B（BDNF-TrkB）信号通路可抑制脊髓损伤大鼠跑步机训练后神经功能恢复的促进作用。
Blocking of BDNF-TrkB signaling inhibits the promotion effect of neurological function recovery after treadmill training in rats with spinal cord injury.
作者信息
Li Xiangzhe, Wu Qinfeng, Xie Caizhong, Wang Can, Wang Qinghua, Dong Chuanming, Fang Lu, Ding Jie, Wang Tong
机构信息
Rehabilitation Medicine Center, The First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.
Rehabilitation Medicine Center, Suzhou Science & Technology Town Hospital, 215153, Suzhou, Jiangsu, China.
出版信息
Spinal Cord. 2019 Jan;57(1):65-74. doi: 10.1038/s41393-018-0173-0. Epub 2018 Jul 12.
STUDY DESIGN
Experimental study.
OBJECTIVES
To investigate the role of BDNF-TrkB signaling that promotes the recovery of neurological function in rats with incomplete spinal cord injury (SCI) after treadmill training (TT).
SETTING
Rehabilitation Medicine Center of the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
METHODS
Forty rats were divided into five groups: (i) Sham; (ii) SCI and phosphate-buffered saline (PBS) (SCI/PBS); (iii) SCI-TT/PBS; (iv) SCI/TrkB-IgG; and (v) SCI-TT/TrkB-IgG. The intrathecal catheter and T10 contusion SCI model was established. At 7-day post SCI, the BDNF-TrkB signaling was blocked by TrkB-IgG. Exercise began at 8th day after SCI and continued for 4 weeks. The BBB scale and motor-evoked potential (MEP) were used for the evaluation of the locomotor functions. The BDNF/TrkB, PSD-95, SYP synthesis, and neuroprotective effect was determined by western blot, Nissl, or immunohistochemistry staining.
RESULTS
The expression of BDNF and TrkB in the SCI-TT/PBS group was 1.46 ± 0.09 and 1.70 ± 0.22, respectively, higher than that in SCI/PBS group (0.51 ± 0.04 and 0.76 ± 0.07, respectively), relative to the Sham group. The BBB scores in the Sham, SCI/PBS, SCI-TT/PBS, SCI/TrkB-IgG, and SCI-TT/TrkB-IgG groups were 21.00 ± 0.00, 7.63 ± 0.74, 12.13 ± 1.36, 7.88 ± 0.64, and 8.75 ± 0.88, respectively. The percentages of MEP responders/non-responders were 100, 0, 75, 0, and 50%. The MEP latencies in Sham, SCI-TT/PBS, and SCI-TT/TrkB-IgG groups were 6.65 ± 0.19, 13.32 ± 2.95, and 19.55 ± 4.55 ms, respectively. The number of NeuN neurons, the cell body area of motor neurons, PSD-95, and SYP expression in the SCI-TT/PBS group was significantly higher than that in the SCI/PBS, SCI/TrkB-IgG, and SCI-TT/TrkB-IgG groups.
CONCLUSION
The BDNF-TrkB signaling is a critical pathway in exercise training that promotes the recovery of neurological function in rats with incomplete SCI.
研究设计
实验性研究。
目的
探讨脑源性神经营养因子（BDNF）-酪氨酸激酶受体B（TrkB）信号通路在不完全性脊髓损伤（SCI）大鼠跑步机训练（TT）后促进神经功能恢复中的作用。
地点
中国南京医科大学第一附属医院康复医学中心。
方法
将40只大鼠分为五组：（i）假手术组；（ii）SCI+磷酸盐缓冲液（PBS）组（SCI/PBS）；（iii）SCI-TT/PBS组；（iv）SCI/TrkB-IgG组；（v）SCI-TT/TrkB-IgG组。建立鞘内导管及T10挫伤性SCI模型。SCI后7天，用TrkB-IgG阻断BDNF-TrkB信号通路。运动训练于SCI后第8天开始，持续4周。采用BBB评分和运动诱发电位（MEP）评估运动功能。通过蛋白质免疫印迹法、尼氏染色或免疫组织化学染色检测BDNF/TrkB、突触后密度蛋白95（PSD-95）、突触素（SYP）的合成及神经保护作用。
结果
相对于假手术组，SCI-TT/PBS组中BDNF和TrkB的表达分别为1.46±0.09和1.70±0.22，高于SCI/PBS组（分别为0.51±0.04和0.76±0.07）。假手术组、SCI/PBS组、SCI-TT/PBS组、SCI/TrkB-IgG组和SCI-TT/TrkB-IgG组的BBB评分分别为21.00±0.00、7.63±0.74、12.13±1.36、7.88±0.64和8.75±0.88。MEP反应者/无反应者的百分比分别为100%、0、75%、0和50%。假手术组、SCI-TT/PBS组和SCI-TT/TrkB-IgG组的MEP潜伏期分别为6.65±0.19、13.32±2.95和19.55±4.55毫秒。SCI-TT/PBS组NeuN神经元数量、运动神经元胞体面积、PSD-95和SYP表达均显著高于SCI/PBS组、SCI/TrkB-IgG组和SCI-TT/TrkB-IgG组。
结论
BDNF-TrkB信号通路是运动训练促进不完全性SCI大鼠神经功能恢复的关键途径。
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