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Neural Regeneration Research 2022年第6期17卷 1343-1347页

作者： Wei Pi Ci Li Meng zhang Wei zhang pei-xun zhang Department of Orthopedics and Trauma Peking University People’s HospitalPeking UniversityBeijingChina Key Laboratory of Trauma and Neural Regeneration Peking UniversityBeijingChina National Center for Trauma Medicine BeijingChina

Studies have shown that myelin-associated glycoprotein(MAG)can inhibit axon regeneration after nerve injury.However,the effects of MAG on neuroma formation after peripheral nerve injury remain poorly understood.In this study,local injection of MAG combined with nerve cap made of chitin conduit was used to intervene with the formation of painful neuroma after sciatic nerve transfection in rats.After 8 weeks of combined treatment,the autotomy behaviors were reduced in rats subjected to sciatic nerve transfection,the mRNA expression of nerve growth factor,a pain marker,in the proximal nerve stump was decreased,the density of regenerated axons was decreased,the thickness of the myelin sheath was increased,and the ratio of unmyelinated to myelinated axons was reduced.Moereover,the percentage of collagen fiber area and the percentage of fibrosis marker alpha-smooth muscle actin positive staining area in the proximal nerve stump were decreased.The combined treatment exhibited superior effects in these measures to chitin conduit treatment alone.These findings suggest that MAG combined with chitin conduit synergistically inhibits the formation of painful neuroma after sciatic nerve transection and alleviates neuropathic pain.This study was approved by the Animal Ethics Committee of Peking University People’s Hospital(approval No.2019PHE027)on December 5,2019.

关键词： autotomy axon chitin conduit fibrosis myelin-associated glycoprotein painful neuroma peripheral nerve regeneration

An electroencephalography-based human-machine interface combined with contralateral C7 transfer in the treatment of brachial plexus injury

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Neural Regeneration Research 2022年第12期17卷 2600-2605页

作者： Meng zhang Ci Li Song-Yang Liu Feng-Shi zhang pei-xun zhang Department of Orthopedics and Trauma Peking University People’s HospitalBeijingChina Key Laboratory of Trauma and Neural Regeneration Peking UniversityBeijingChina National Center for Trauma Medicine BeijingChina

Transferring the contralateral C7 nerve root to the median or radial nerve has become an important means of repairing brachial plexus nerve injury.However,outcomes have been disappointing.Electroencephalography(EEG)-based human-machine interfaces have achieved promising results in promoting neurological recovery by controlling a distal exoskeleton to perform functional limb exercises early after nerve injury,which maintains target muscle activity and promotes the neurological rehabilitation effect.This review summarizes the progress of research in EEG-based human-machine interface combined with contralateral C7 transfer repair of brachial plexus nerve injury.Nerve transfer may result in loss of nerve function in the donor area,so only nerves with minimal impact on the donor area,such as the C7 nerve,should be selected as the donor.Single tendon transfer does not fully restore optimal joint function,so multiple functions often need to be reestablished simultaneously.Compared with traditional manual rehabilitation,EEG-based human-machine interfaces have the potential to maximize patient initiative and promote nerve regeneration and cortical remodeling,which facilitates neurological recovery.In the early stages of brachial plexus injury treatment,the use of an EEG-based human-machine interface combined with contralateral C7 transfer can facilitate postoperative neurological recovery by making full use of the brain’s computational capabilities and actively controlling functional exercise with the aid of external machinery.It can also prevent disuse atrophy of muscles and target organs and maintain neuromuscular junction effectiveness.Promoting cortical remodeling is also particularly important for neurological recovery after contralateral C7 transfer.Future studies are needed to investigate the mechanism by which early movement delays neuromuscular junction damage and promotes cortical remodeling.Understanding this mechanism should help guide the development of neurological rehabilitation strategies for patients with

关键词： arm injuries brachial plexus brain-computer interfaces nerve transfer nerve regeneration nerve tissue neurofeedback neurological rehabilitation user-computer interface

Brain functional remodeling caused by sciatic nerve transposition repair in rats identified by multiplemodel resting-state blood oxygenation level-dependent functional magnetic resonance imaging analysis

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Neural Regeneration Research 2022年第2期17卷 418-426页

作者： Yu-Song Yuan Hai-Lin Xu Zhong-Di Liu Yu-Hui Kou Bo Jin pei-xun zhang Department of Trauma and Orthopedics Peking University People’s HospitalPeking UniversityBeijingChina Key Laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijingChina National Center for Trauma Medicine BeijingChina

Lower extremity nerve transposition repair has become an important treatment strategy for peripheral nerve injury;however, brain changes caused by this surgical procedure remain unclear. In this study, the distal stump of the right sciatic nerve in a rat model of sciatic nerve injury was connected to the proximal end of the left sciatic nerve using a chitin conduit. Neuroelectrophysiological test showed that the right lower limb displayed nerve conduction, and the structure of myelinated nerve fibers recovered greatly. Muscle wet weight of the anterior tibialis and gastrocnemius recovered as well. Multiple-model resting-state blood oxygenation level-dependent functional magnetic resonance imaging analysis revealed functional remodeling in multiple brain regions and the re-establishment of motor and sensory functions through a new reflex arc. These findings suggest that sciatic nerve transposition repair induces brain functional remodeling. The study was approved by the Ethics Committee of Peking University People's Hospital on December 9, 2015(approval No. 2015-50).

关键词： brain connectivity brain network fALFF MRI nerve transposition repair peripheral nerve injury ReHo remodeling

Sustained release of exosomes loaded into polydopamine-modified chitin conduits promotes peripheral nerve regeneration in rats

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Neural Regeneration Research 2022年第9期17卷 2050-2057页

作者： Ci Li Song-Yang Liu Meng zhang Wei Pi Bo Wang Qi-Cheng Li Chang-Feng Lu pei-xun zhang Department of Orthopedics and Trauma Peking University People’s HospitalBeijingChina Key Laboratory of Trauma and Neural Regeneration Ministry of EducationBeijingChina National Center for Trauma Medicine BeijingChina Department of Orthopedics Beijing Jishuitan HospitalBeijingChina

Exosomes derived from mesenchymal stem cells are of therapeutic interest because of their important role in intracellular communication and biological regulation.On the basis of previously studied nerve conduits,we designed a polydopamine-modified chitin conduit loaded with mesenchymal stem cell-derived exosomes that release the exosomes in a sustained and stable manner.In vitro experiments revealed that rat mesenchymal stem cell-derived exosomes enhanced Schwann cell proliferation and secretion of neurotrophic and growth factors,increased the expression of Jun and Sox2 genes,decreased the expression of Mbp and Krox20 genes in Schwann cells,and reprogrammed Schwann cells to a repair phenotype.Furthermore,mesenchymal stem cell-derived exosomes promoted neurite growth of dorsal root ganglia.The polydopamine-modified chitin conduits loaded with mesenchymal stem cell-derived exosomes were used to bridge 2 mm rat sciatic nerve defects.Sustained release of exosomes greatly accelerated nerve healing and improved nerve function.These findings confirm that sustained release of mesenchymal stem cell-derived exosomes loaded into polydopamine-modified chitin conduits promotes the functional recovery of injured peripheral nerves.

关键词： exosome mesenchymal stem cells modification strategy nerve conduits peripheral nerve injury peripheral nerve regeneration polydopamine reprogramming state Schwann cells sustained release

Polydopamine-modified chitin conduits with sustained release of bioactive peptides enhance peripheral nerve regeneration in rats

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Neural Regeneration Research 2022年第11期17卷 2544-2550页

作者： Ci Li Song-Yang Liu Li-Ping Zhou Tian-Tian Min Meng zhang Wei Pi Yong-Qiang Wen pei-xun zhang Department of Orthopedics and Trauma Peking University People’s HospitalBeijingChina Key Laboratory of Trauma and Neural Regeneration Ministry of EducationBeijingChina National Center for Trauma Medicine BeijingChina Beijing Key Laboratory for Bioengineering and Sensing Technology School of Chemistry and Biological EngineeringUniversity of Science and Technology BeijingBeijingChina

The introduction of neurotrophic factors into injured peripheral nerve sites is beneficial to peripheral nerve regeneration.However,neurotrophic facto rs are rapidly degraded in vivo and obstruct axonal regeneration when used at a supraphysiological dose,which limits their clinical benefits.Bioactive mimetic peptides have been developed to be used in place of neurotrophic factors because they have a similar mode of action to the original growth fa ctors and can activate the equivalent receptors but have simplified sequences and structures.In this study,we created polydopamine-modified chitin conduits loaded with brain-derived neurotrophic factor mimetic peptides and vascular endothelial growth fa ctor mimetic peptides(Chi/PDA-Ps).We found that the Chi/PDA-Ps conduits were less cytotoxic in vitro than chitin conduits alone and provided sustained release of functional peptides.In this study,we evaluated the biocompatibility of the Chi/P DA-Ps conduits.Brain-derived neurotrophic factor mimetic peptide and vascular endothelial growth fa ctor mimetic peptide synergistically promoted prolife ration of Schwann cells and secretion of neurotrophic factors by Schwann cells and attachment and migration of endothelial cells in vitro.The Chi/P DA-Ps conduits were used to bridge a 2 mm gap between the nerve stumps in rat models of sciatic nerve injury.We found that the application of Chi/PDA-Ps conduits could improve the motor function of rats and reduce gastrocnemius atrophy.The electrophysiological results and the microstructure of regenerative nerves showed that the nerve conduction function and re myelination was further resto red.These findings suggest that the Chi/PDA-Ps conduits have great potential in peripheral nerve injury repair.

关键词： angiogenesis bioactive peptides nerve repair neurotrophic factor peripheral nerve injury peripheral nerve regeneration polydopamine surface modification synergistic effects tissue engineering

The anatomical,electrophysiological and histological observations of muscle contraction units in rabbits:a new perspective on nerve injury and regeneration

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Neural Regeneration Research 2022年第1期17卷 228-232页

作者： Ting-Min Xu Bo Chen Zong-Xue Jin Xiao-Feng Yin pei-xun zhang Bao-Guo Jiang Department of Trauma and Orthopedics Peking University People’s HospitalBeijingChina Key Laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijingChina Trauma Center Peking University People’s HospitalBeijingChina National Trauma Medical Center BeijingChina Department of Rehabilitation Peking University People’s HospitalBeijingChina

In the conventional view a muscle is composed of intermediate structures before its further division into microscopic muscle fibers.Our experiments in mice have confirmed this intermediate structure is composed of the lamella cluster formed by motor endplates,the innervating nerve branches and the corresponding muscle fibers,which can be viewed as an independent structural and functional unit.In this study,we verified the presence of these muscle construction units in rabbits.The results showed that the muscular branch of the femoral nerve sent out 4–6 nerve branches into the quadriceps and the tibial nerve sent out 4–7 nerve branches into the gastrocnemius.When each nerve branch of the femoral nerve was stimulated from the most lateral to the medial,the contraction of the lateral muscle,intermediate muscle and medial muscle of the quadriceps could be induced by electrically stimulating at least one nerve branch.When stimulating each nerve branch of the tibial nerve from the lateral to the medial,the muscle contraction of the lateral muscle 1,lateral muscle 2,lateral muscle 3 and medial muscle of the gastrocnemius could be induced by electrically stimulating at least one nerve branch.Electrical stimulation of each nerve branch resulted in different electromyographical waves recorded in different muscle subgroups.Hematoxylin-eosin staining showed most of the nerve branches around the neuromuscular junctions consisted of one individual neural tract,a few consisted of two or more neural tracts.The muscles of the lower limb in the rabbit can be subdivided into different muscle subgroups,each innervated by different nerve branches,thereby allowing much more complex muscle activities than traditionally stated.Together,the nerve branches and the innervated muscle subgroups can be viewed as an independent structural and functional unit.This study was approved by the Animal Ethics Committee of Peking University People’s Hospital(approval No.2019 PHE027)on October 20,2019.

关键词： anatomy electrophysiology femoral nerve hematoxylin-eosin staining gastrocnemius motor endplate muscle contraction unit peripheral nerve quadriceps rabbit skeletal muscle tibial nerve

Cortical plasticity and nerve regeneration after peripheral nerve injury

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Neural Regeneration Research 2021年第8期16卷 1518-1523页

作者： Ci Li Song-Yang Liu Wei Pi pei-xun zhang Department of Orthopedics and Trauma Peking University People’s HospitalBeijingChina Key Laboratory of Trauma and Neural Regeneration Peking UniversityBeijingChina National Center for Trauma Medicine BeijingChina

With the development of neuroscience, substantial advances have been achieved in peripheral nerve regeneration over the past decades. However, peripheral nerve injury remains a critical public health problem because of the subsequent impairment or absence of sensorimotor function. Uncomfortable complications of peripheral nerve injury, such as chronic pain, can also cause problems for families and society. A number of studies have demonstrated that the proper functioning of the nervous system depends not only on a complete connection from the central nervous system to the surrounding targets at an anatomical level, but also on the continuous bilateral communication between the two. After peripheral nerve injury, the interruption of afferent and efferent signals can cause complex pathophysiological changes, including neurochemical alterations, modifications in the adaptability of excitatory and inhibitory neurons, and the reorganization of somatosensory and motor regions. This review discusses the close relationship between the cerebral cortex and peripheral nerves. We also focus on common therapies for peripheral nerve injury and summarize their potential mechanisms in relation to cortical plasticity. It has been suggested that cortical plasticity may be important for improving functional recovery after peripheral nerve damage. Further understanding of the potential common mechanisms between cortical reorganization and nerve injury will help to elucidate the pathophysiological processes of nerve injury, and may allow for the reduction of adverse consequences during peripheral nerve injury recovery. We also review the role that regulating reorganization mechanisms plays in functional recovery, and conclude with a suggestion to target cortical plasticity along with therapeutic interventions to promote peripheral nerve injury recovery.

关键词： cortical plasticity injury mechanisms nerve transfer neurorrhaphy peripheral nerve phantom limb pain recovery regeneration treatment

Anterior subcutaneous transposition of the ulnar nerve improves neurological function in patients with cubital tunnel syndrome

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Neural Regeneration Research 2015年第10期10卷 1690-1695页

作者： Wei Huang pei-xun zhang zhang Peng Feng Xue Tian-bing Wang Bao-guo Jiang Department of Trauma and Orthopedics Peking University People’s Hospital

Although several surgical procedures exist for treating cubital tunnel syndrome, the best surgical option remains controversial. To evaluate the efficacy of anterior subcutaneous transposition of the ulnar nerve in patients with moderate to severe cubital tunnel syndrome and to analyze prognostic factors, we retrospectively reviewed 62 patients（65 elbows） diagnosed with cubital tunnel syndrome who underwent anterior subcutaneous transposition. Preoperatively, the initial severity of the disease was evaluated using the Mc Gowan scale as modified by Goldberg： 18 patients（28%） had grade IIA neuropathy, 20（31%） had grade IIB, and 27（42%） had grade III. Postoperatively, according to the Wilson ＆ Krout criteria, treatment outcomes were excellent in 38 patients（58%）, good in 16（25%）, fair in 7（11%）, and poor in 4（6%）, with an excellent and good rate of 83%. A negative correlation was found between the preoperative Mc Gowan grade and the postoperative Wilson ＆ Krout score. The patients having fair and poor treatment outcomes had more advanced age, lower nerve conduction velocity, and lower action potential amplitude compared with those having excellent and good treatment outcomes. These results suggest that anterior subcutaneous transposition of the ulnar nerve is effective and safe for the treatment of moderate to severe cubital tunnel syndrome, and initial severity, advancing age, and electrophysiological parameters can affect treatment outcome.

关键词： nerve regeneration peripheral nerve injury ulnar nerve compression syndrome age motor nerve conduction velocity electrophysiology sensory nerve conduction velocity modified Mc Gowan scale Wilson ＆ Krout criteria anterior transposition ulnar nerve NSFC grant neural regeneration

Qian-Zheng-San promotes regeneration after sciatic nerve crush injury in rats

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Neural Regeneration Research 2019年第4期14卷 683-691页

作者： Zhi-Yong Wang Li-Hua Qin Wei-Guang zhang pei-xun zhang Bao-Guo Jiang Department of Anatomy and Histo-embryology School of Basic Medical Sciences Peking University Department of Trauma and Orthopedics Peking University People's Hospital

Qian-Zheng-San, a traditional Chinese prescription consisting of Typhonii Rhizoma, Bombyx Batryticatus, Scorpio, has been found to play an active therapeutic role in central nervous system diseases. However, it is unclear whether Qian-Zheng-San has therapeutic value for peripheral nerve injury. Therefore, we used Sprague-Dawley rats to investigate this. A sciatic nerve crush injury model was induced by clamping the right sciatic nerve. Subsequently, rats in the treatment group were administered 2 mL Qian-Zheng-San(1.75 g/mL) daily as systemic therapy for 1, 2, 4, or 8 weeks. Rats in the control group were not administered Qian-Zheng-San. Rats in sham group did not undergo surgery and systemic therapy. Footprint analysis was used to assess nerve motor function. Electrophysiological experiments were used to detect nerve conduction function. Immunofluorescence staining was used to assess axon counts and morphological analysis. Immunohistochemical staining was used to observe myelin regeneration of the sciatic nerve and the number of motoneurons in the anterior horn of the spinal cord. At 2 and 4 weeks postoperatively, the sciatic nerve function index, nerve conduction velocity, the number of distant regenerated axons and the axon diameter of the sciatic nerve increased in the Qian-Zheng-San treatment group compared with the control group. At 2 weeks postoperatively, nerve fiber diameter, myelin thickness, and the number of motor neurons in the lumbar spinal cord anterior horn increased in the Qian-Zheng-San treatment group compared with the control group. These results indicate that QianZheng-San has a positive effect on peripheral nerve regeneration.

关键词： nerve regeneration traditional Chinese medicine crush injury peripheral nerve regeneration nerve conduction velocity sciatic function index nerve injury nerve repair formula scorpion neural regeneration

Short-term observations of the regenerative potential of injured proximal sensory nerves crossed with distal motor nerves

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Neural Regeneration Research 2017年第7期12卷 1172-1176页

作者： Xiu-xiu zhang Yu-hui Kou Xiao-feng Yin Bao-guo Jiang pei-xun zhang Department of Orthopedics and Trauma Peking University People's Hospital Beijing China

Motor nerves and sensory nerves conduct signals in different directions and function in different ways.In the surgical treatment of peripheral nerve injuries,the best prognosis is obtained by keeping the motor and sensory nerves separated and repairing the nerves using the suture method.However,the clinical consequences of connections between sensory and motor nerves currently remain unknown.In this study,we analyzed the anatomical structure of the rat femoral nerve,and observed the motor and sensory branches of the femoral nerve in the quadriceps femoris.After ligation of the nerves,the proximal end of the sensory nerve was connected with the distal end of the motor nerve,followed by observation of the changes in the newly-formed regenerated nerve fibers.Acetylcholinesterase staining was used to distinguish between the myelinated and unmyelinated motor and sensory nerves.Denervated muscle and newly formed nerves were compared in terms of morphology,electrophysiology and histochemistry.At 8 weeks after connection,no motor nerve fibers were observed on either side of the nerve conduit and the number of nerve fibers increased at the proximal end.The proportion of newly-formed motor and sensory fibers was different on both sides of the conduit.The area occupied by autonomic nerves in the proximal regenerative nerve was limited,but no distinct myelin sheath was visible in the distal nerve.These results confirm that sensory and motor nerves cannot be effectively connected.Moreover,the change of target organ at the distal end affects the type of nerves at the proximal end.

关键词： nerve regeneration nerve remodeling peripheral nerve acetylcholinesterase staining muscle denervation neural anastomosis nerveconduit neural regeneration