中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (6): 1278-1285.doi: 10.4103/1673-5374.327359

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

出血性脑卒中后肢偏瘫的个体化神经修复

  

  • 出版日期:2022-06-15 发布日期:2021-12-17

L4-to-L4 nerve root transfer for hindlimb hemiplegia after hypertensive intracerebral hemorrhage

Teng-Da Qian1, #, Xi-Feng Zheng2, #, Jing Shi3, Tao Ma3, Wei-Yan You4, Jia-Huan Wu4, Bao-Sheng Huang5, Yi Tao6, Xi Wang7, Ze-Wu Song7, Li-Xin Li7, *   

  1. 1Department of Neurosurgery, Jintan Hospital, Affiliated Hospital of Jiangsu Vocational College of Medicine, Jintan, Jiangsu Province, China; 2Department of Gastroenterology, Jintan Hospital, Affiliated Hospital of Jiangsu Vocational College of Medicine, Jintan, Jiangsu Province, China; 3Department of Neurosurgery, Changzhou First People’s Hospital, Suzhou University, Changzhou, Jiangsu Province, China; 4Deparment of Neurobiology, Basic Medical College, Nanjing Medical University, Nanjing, Jiangsu Province, China; 5Department of Neurosurgery, Sir Run Run Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu Province, China; 6Department of Neurosurgery, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China; 7Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
  • Online:2022-06-15 Published:2021-12-17
  • Contact: Li-Xin Li, PhD, lilixin2@hotmail.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81171147 (to LXL); “Key Medical Talents of Qiangwei Project” Research Foundation of Health Department of Jiangsu Province, No. ZDRCA2016010 (to LXL); “Xingwei Project” Key Personal Medical Research Foundation of Health Department of Jiangsu Province, No. RC201156 (to LXL); Jiangsu Province’s Key Discipline of Medicine, No. XK201117 (to LXL); the Priority Academic Program Development of Jiangsu Higher Education Institutions, PAPD (to LXL); the Natural Science Foundation of Jiangsu Province, No. BK20171064 (to BSH). 

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摘要：

高血压脑出血引起的肢体偏瘫目前尚未有效治疗措施，考虑到腰丛神经根中的L4神经根发出的分支可支配下肢前、后肌群的运动，作者设计了一种新的神经修复方法，通过向内囊后肢注射自体血制作高血压脑出血下肢偏瘫大鼠模型，将大鼠模型健侧L4神经根移位与患侧L4神经根相连接吻合，驱动下肢伸肌和屈肌运动，以此验证此方法是否可以恢复高血压脑出血后瘫痪大鼠下肢的灵活运动。结果显示：(1)在走横杆/栏梯实验中，大鼠起初滑脱率高，但后期，则表现出更大的步态准确增量。(2)术后17周，大鼠踝关节动作准确率约为58.2%，瘫痪侧下肢可进行踝关节运动。(3)术后9周，在逆行性示踪实验中可见，大鼠支配L4-L4再生神经根的脊髓前角出现大量荧光金染色的运动神经元，而且通过组织学和超微结构观察可发现脊髓前角运动神经元的轴突再生现象。(4)最后通过肌电图及足印迹分析结果发现，大鼠失神经支配的下肢肌肉重新获得可靠的神经支配以及有效的肌力改善。(5)上述数据显示，对高血压脑出血后偏瘫而言，L4-L4移植(患侧L4神经根移位与健侧L4神经根相连接吻合)可以改善下肢大关节的运动功能，尤其是可有效恢复远端踝关节的运动功能，证实了此方法可以有效修复高血压脑出血后下肢瘫痪。

https://orcid.org/0000-0002-9404-5538 (Li-Xin Li) 

关键词: 中枢性偏瘫, 端-端吻合, 功能再生, 高血压脑出血, L4神经根, 神经化, 神经再生, 大鼠模型, 神经重支配, 精细功能修复

Abstract: There is no effective treatment for hemiplegia after hypertensive intracerebral hemorrhage. Considering that the branches of L4 nerve roots in the lumbar plexus root control the movement of the lower extremity anterior and posterior muscles, we investigated a potential method of nerve repair using the L4 nerve roots. Rat models of hindlimb hemiplegia after a hypertensive intracerebral hemorrhage were established by injecting autogenous blood into the posterior limb of internal capsule. The L4 nerve root on the healthy side of model rats was transferred and then anastomosed with the L4 nerve root on the affected side to drive the extensor and flexor muscles of the hindlimbs. We investigated whether this method can restore the flexible movement of the hindlimbs of paralyzed rats after hypertensive intracerebral hemorrhage. In a beam-walking test and ladder rung walking task, model rats exhibited an initial high number of slips, but improved in accuracy on the paretic side over time. At 17 weeks after surgery, rats gained approximately 58.2% accuracy from baseline performance and performed ankle motions on the paretic side. At 9 weeks after surgery, a retrograde tracing test showed a large number of fluoro-gold-labeled motoneurons in the left anterior horn of the spinal cord that supports the L4-to-L4 nerve roots. In addition, histological and ultramicrostructural findings showed axon regeneration of motoneurons in the anterior horn of the spinal cord. Electromyography and paw print analysis showed that denervated hindlimb muscles regained reliable innervation and walking coordination improved. These findings suggest that the L4-to-L4 nerve root transfer method for the treatment of hindlimb hemiplegia after hypertensive intracerebral hemorrhage can improve the locomotion of hindlimb major joints, particularly of the distal ankle. Findings from study support that the L4-to-L4 nerve root transfer method can effectively repair the hindlimb hemiplegia after hypertensive intracerebral hemorrhage. All animal experiments were approved by the Animal Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (No. IACUC-1906009) in June 2019. 

Key words: central hemiplegia, end-to-end anastomosis, functional regeneration, hypertensive intracerebral hemorrhage, L4 nerve root, neural regeneration, neurotization, rat model, reinnervation, skilled restoration

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