任务导向性康复训练对小鼠脊髓损伤后神经回路可塑性及前肢运动功能的影响

doi:10.3969/j.issn.1006-9771.2020.10.006

《中国康复理论与实践》 ›› 2020, Vol. 26 ›› Issue (10): 1152-1160.doi: 10.3969/j.issn.1006-9771.2020.10.006

任务导向性康复训练对小鼠脊髓损伤后神经回路可塑性及前肢运动功能的影响

潘璐¹,谭波涛¹,罗美玲¹,刘媛²,伍亚民²,虞乐华¹,殷樱¹()

1.重庆医科大学附属第二医院康复医学科,重庆市 400010
2.陆军军医大学特色医学中心（大坪医院）特殊环境战伤防治研究室,创伤、烧伤与复合伤国家重点实验室,重庆市 400042

收稿日期:2020-01-19 修回日期:2020-02-05 出版日期:2020-10-25 发布日期:2020-10-29
通讯作者: 殷樱 E-mail:300735@cqmu.edu.cn
作者简介:潘璐(1995-),女,汉族,重庆市人,硕士研究生,主要研究方向：神经康复。
基金资助:
1.国家自然科学基金项目(81702221);2.重庆市自然科学基金项目(cstc2018jcyjAX0180);重庆市自然科学基金项目(cstc2019jcyj-msxmX0195);3.重庆市渝中区基础研究与前沿探索项目(20180121)

Effect of Task-based Rehabilitation Training on Neural Circuit Plasticity and Forelimb Motor Function post Spinal Cord Injury in Mice

PAN Lu¹,TAN Bo-tao¹,LUO Mei-ling¹,LIU Yuan²,WU Ya-min²,YU Le-hua¹,YIN Ying¹()

1. Department of Rehabilitation Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
2. State Key Laboratory of Trauma, Burns and Combined Injury, Department of Research Institute of Surgery, Daping Hospital, the Army Medical University, Chongqing 400042, China

Received:2020-01-19 Revised:2020-02-05 Published:2020-10-25 Online:2020-10-29
Contact: YIN Ying E-mail:300735@cqmu.edu.cn
Supported by:
National Science Foundation of China(81702221);Natural Science Foundation of Chongqing(cstc2018jcyjAX0180);Natural Science Foundation of Chongqing(cstc2019jcyj-msxmX0195);Fundamental Research and Frontier Exploration Foundation of Yuzhong, Chongqing(20180121)

摘要/Abstract

摘要：

目的探讨任务导向性康复训练对小鼠C₅脊髓损伤后神经回路可塑性及前肢运动功能恢复的影响。
方法健康成年C75/BL小鼠21只随机数字表法分为假手术组、模型组、训练组,每组7只。模型组和训练组对C₅脊髓进行左背侧及背外侧束钳夹损伤,假手术组仅剔除椎板。术后4周,训练组接受左侧前肢任务导向性康复训练4周。术前,术后3 d、2周、4周、6周和8周行水平楼梯和圆筒攀爬探索测试。术后6周,采用生物素化葡聚糖胺(BDA)顺行示踪观察皮质脊髓束的轴突。术后8周,运动诱发电位检测左前肢的神经传导情况;免疫荧光双标BDA/神经元核特异蛋白(NeuN),观察病灶上段灰质前角内轴突出芽及与神经元的结构关系;免疫荧光双标NeuN/突触素I(Synapsin I),观察病灶处灰质前角内突触素的表达情况。
结果术后8周,模型组P1、N1潜伏期长于假手术组(P < 0.05),训练组短于模型组( P < 0.05)。术后各时间点,与假手术组比较,模型组和训练组左前肢错误率升高,使用率下降( P < 0.05);与模型组比较,术后6周和8周,训练组左前肢错误率降低( P < 0.05),术后8周,训练组左前肢使用率升高( P < 0.05)。与模型组比较,训练组病灶上段灰质前角内轴突出芽增加,出芽轴突多与神经元共区域,Synapsin I表达增加( P < 0.05)。
结论任务导向性康复训练能促进脊髓损伤后局部神经回路可塑性变化,改善前肢运动功能。

关键词: 脊髓损伤, 任务导向性康复训练, 神经可塑性, 前肢, 运动功能, 小鼠

Abstract:

Objective To explore the effect of task-based rehabilitative training on neural circuit plasticity and forelimb motor function after C₅ spinal cord injury in mice.
Methods A total of 21 healthy C57/BL mice were randomly and equally divided into sham group, model group and training group. The model was established by left C₅ spinal cord crush injury. The lamina was removed without damaging the spinal cord in the sham group. Four weeks after injury, the training group received task-based rehabilitative training for four weeks. The horizontal ladder and rearing tests were used to assess motor function for forelimb before injury, and three days, two weeks, four weeks, six weeks and eight weeks after injury. The axons of the corticospinal tract in all mice were observed six weeks after injury by using biotinylated dextran amin (BDA) anterograde tracing. Eight weeks after injury, motor-evoked potential was applied to measure nerve conduction velocities in forelimb, while the axon sprouting and syntagmatic relation of neuron in the anterior horn of gray matter above lesion were observed by immunofluorescence double-labeling of BDA/neuron-specific nuclei protein (NeuN); the expression of Synapsin in the anterior horn of gray matter at lesion was observed by immunofluorescence double-labeling of NeuN/Synapsin I.
Results Eight weeks after injury, the latency of P1 and N1 was longer in the model group than in the sham group ( P < 0.05), and was shorter in the training group than in the model group ( P < 0.05). Compared with the sham group, the error rate of left forelimb increased, and the usage rate decreased ( P < 0.05) in the model group and the training group; compared with the model group, the error rate of left forelimb decreased six weeks and eight weeks after injury ( P < 0.05), and the usage rate increased eight weeks after injury ( P < 0.05) in the treatment group. Compared with the model group, more axon sprouting co-localized with neurons in the anterior horn of gray matter above lesion ( P < 0.05), and the expression of Synapsin I increased in the training group ( P < 0.05).
Conclusion Task-based rehabilitative training could promote the neural circuit plasticity and improve the motor function of forelimb after spinal cord injury in mice.

Key words: spinal cord injury, task-based rehabilitative training, neuroplasticity, forelimb, motor function, mice

中图分类号:

R651.2

潘璐,谭波涛,罗美玲,刘媛,伍亚民,虞乐华,殷樱. 任务导向性康复训练对小鼠脊髓损伤后神经回路可塑性及前肢运动功能的影响[J]. 《中国康复理论与实践》, 2020, 26(10): 1152-1160.

PAN Lu,TAN Bo-tao,LUO Mei-ling,LIU Yuan,WU Ya-min,YU Le-hua,YIN Ying. Effect of Task-based Rehabilitation Training on Neural Circuit Plasticity and Forelimb Motor Function post Spinal Cord Injury in Mice[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2020, 26(10): 1152-1160.

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组别	n	P1	N1
假手术组	7	5.300±0.265	6.343±0.658
模型组	7	7.986±1.404^a	9.386±1.826^a
训练组	7	5.886±0.471^b	6.943±0.820^b
F值		18.508	12.285
P值		< 0.001	< 0.001

组别	n	术前	术后3 d	术后2周	术后4周	术后6周	术后8周
假手术组	7	1.7±1.0	1.1±0.9	1.6±0.9	1.3±1.5	1.6±1.6	1.1±0.5
模型组	7	2.2±1.7	31.8±6.3^a	16.5±4.8^a	12.8±4.0^a	22.3±9.3^a	15.2±2.7^a
训练组	7	2.1±1.6	27.4±3.1^a	18.1±2.3^a	10.3±5.1^a	11.8±3.6^a,b	8.8±2.9^a,b
F值		0.355	115.523	60.251	17.240	22.227	65.328
P值		0.706	< 0.001	< 0.001	< 0.001	< 0.001	< 0.001

组别	n	术前	术后3 d	术后2 周	术后4周	术后6周	术后8周
假手术组	7	8.6±6.9	10.0±5.8	12.1±3.9	12.8±4.9	10.8±8.4	10.8±4.5
模型组	7	11.4±6.9	1.4±3.8^a	3.6±6.2^a	5.0±5.0^a	4.3±4.5	3.6±4.8^a
训练组	7	10.0±7.1	2.9±4.9^a	2.9±4.9^a	4.1±5.3^a	8.6±6.9	14.3±5.3^b
F值		0.265	6.200	7.136	6.138	1.629	8.750
P值		0.770	0.009	0.005	0.009	0.224	0.002

组别	n	轴突(a.u. /mm²)	NeuN/BDA(个/mm²)
假手术组	7	267325.286±97575.678	17.143±4.451
模型组	7	768600.857±86511.326	19.143±4.811
训练组	7	1861362.762±771881.369^a,b	33.286±4.990^a,b
F值		32.019	23.964
P值		< 0.001	< 0.001

组别	n	Synapsin I(a.u. /mm²)
假手术组	7	35.545±2.903
模型组	7	15.760±1.469^a
训练组	7	25.080±1.812^a,b
F值		148.354
P值		< 0.001

任务导向性康复训练对小鼠脊髓损伤后神经回路可塑性及前肢运动功能的影响

Effect of Task-based Rehabilitation Training on Neural Circuit Plasticity and Forelimb Motor Function post Spinal Cord Injury in Mice

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