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Effects of delayed repair of peripheral nerve injury on the spatial distribution of motor endplates in target muscle

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Neural Regeneration Research 2022年第2期17卷 459-464页

作者： Dong-Dong Li Jin Deng Bo Jin Shuai Han Xin-Yi Gu Xue-Feng Zhou Xiao-Feng Yin department of Trauma and orthopedics Peking University People’s HospitalBeijingChina Department of Orthopedics PLA Strategic Support Force Medical CenterBeijingChina

Motor endplates(MEPs) are important sites of information exchange between motor neurons and skeletal muscle, and are distributed in an organized pattern of lamellae in the muscle. Delayed repair of peripheral nerve injury typically results in unsatisfactory functional recovery because of MEP degeneration. In this study, the mouse tibial nerve was transected and repaired with a biodegradable chitin conduit, immediately following or 1 or 3 months after the injury. Fluorescent α-bungarotoxin was injected to label MEPs. Tissue optical clearing combined with light-sheet microscopy revealed that MEPs were distributed in an organized pattern of lamellae in skeletal muscle after delayed repair for 1 and 3 months. However, the total number of MEPs, the number of MEPs per lamellar cluster, and the maturation of single MEPs in gastrocnemius muscle gradually decreased with increasing denervation time. These findings suggest that delayed repair can restore the spatial distribution of MEPs, but it has an adverse effect on the homogeneity of MEPs in the lamellar clusters and the total number of MEPs in the target muscle. The study procedures were approved by the Animal Ethics Committee of the Peking University People's Hospital(approval No. 2019 PHC015) on April 8, 2019.

关键词： degeneration delayed repair lamellar cluster light-sheet microscopy motor endplates peripheral nerve injury three-dimensional distribution tissue optical clearing

Elevated intraspinal pressure in traumatic spinal cord injury is a promising therapeutic target

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Neural Regeneration Research 2022年第8期17卷 1703-1710页

作者： Chao-Hua Yang Zheng-Xue Quan Gao-Ju Wang Tao He Zhi-Yu Chen Qiao-Chu Li Jin Yang Qing Wang Department of Orthopedics The Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan ProvinceChina Department of Orthopedics The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

The currently recommended management for acute traumatic spinal cord injury aims to reduce the incidence of secondary injury and promote functional recovery.Elevated intraspinal pressure(ISP)likely plays an important role in the processes involved in secondary spinal cord injury,and should not be overlooked.However,the factors and detailed time course contributing to elevated ISP and its impact on pathophysiology after traumatic spinal cord injury have not been reviewed in the literature.Here,we review the etiology and progression of elevated ISP,as well as potential therapeutic measures that target elevated ISP.Elevated ISP is a time-dependent process that is mainly caused by hemorrhage,edema,and blood-spinal cord barrier destruction and peaks at 3 days after traumatic spinal cord injury.Duraplasty and hypertonic saline may be promising treatments for reducing ISP within this time window.Other potential treatments such as decompression,spinal cord incision,hemostasis,and methylprednisolone treatment require further validation.

关键词： blood-spinal cord barrier decompression duraplasty durotomy edema hemorrhage intraspinal pressure myelotomy spinal cord injury therapeutic target

Protective effects of Wuwei Xiaodu Drink against chronic osteomyelitis through Foxp3^(+)CD25^(+)CD4^(+) Treg cells via the IL-2/STAT5 signaling pathway

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Chinese Journal of Natural Medicines 2022年第3期20卷 185-193页

作者： HUANG Kai REN Hai-Yong LIN Bing-Yuan LIU Yi-Yang GUO Qiao-Feng Department of Orthopedics Tongde Hospital of Zhejiang ProvinceHangzhou 310012China

To explore the effectiveness and safety of a Chinese medicinal decoction Wuwei Xiaodu Drink(WWXDD)in inhibiting chronic osteomyelitis via regulatory T cells signaling.The effective constitutes of WWXDD and osteomyelitis related genes were screened.Target proteins were cross-validated using the Venny database.GO function and KEGG pathway analysis were performed for target proteins,while pharmacological network was constructed.The bone properties were analyzed by HE staining and the concentrations of immune factors were measured by ELISA.The expression of CTLA-4 and Foxp3 mRNA and STAT5,p-STAT5,CTLA-4 and Foxp3 protein were detected using Real-time PCR and Western blot,respectively.FACS was used to analyze the percentages of cells.A total of 117 genes overlapped between 785 target genes of the active compounds of WWXDD and 912 osteomyelitis related genes.Inflammation-related genes,including IL-6,TNFα,IL-1βand IL-2 showed high connection degree in the drug-compound-disease-target network.GO function and KEGG pathway analysis revealed that 117 intersection genes mainly enriched in virus infection related pathways,immune related pathways and chemokine signaling pathway.Furthermore,the development of chronic osteomyelitis was suppressed in model rats after treatment with WWXDD.Meanwhile,the concentrations of IL-2 and CD4^(+)CD25^(+)Foxp3 Treg perr centages together with the levels of p-STAT5,CTLA-4 and Foxp3 were also down-regulated.Furthermore,IL-2 and WWXDD drug-containing serum exhibited opposite effects on regulating IL-2,IL-10,TGF-β1,Foxp3,CTLA4 and STAT5.In addition,a STAT5 phosphorylation inhibitor suppressed the expression of Foxp3 and CTLA-4.WWXDD can treat chronic osteomyelitis through suppressing the main regulating factors of Tregs and interfere its immunodepression.Our results bring a new solution for chronic osteomyelitis.

关键词： Chronic osteomyelitis Tregs Immunodepression Wuwei Xiaodu Drink

Transplantation of erythropoietin gene-modified neural stem cells improves the repair of injured spinal cord

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Neural Regeneration Research 2015年第9期10卷 1483-1490页

作者： Min-fei Wu Shu-quan Zhang Rui Gu Jia-bei Liu Ye Li Qing-san Zhu Department of Orthopedics the Second Hospital of Jilin University Department of Orthopedics Tianjin Nankai Hospital Department of Orthopedics China-Japan Union Hospital of Jilin University

The protective effects of erythropoietin on spinal Here, the eukaryotic expression plasmid pcDNA3.1 cord injury have not been well described. human erythropoietin was transfected into rat neural stem cells cultured in vitro. A rat model of spinal cord injury was established using a free falling object. In the human erythropoietin-neural stem cells group, transfected neural stem cells were injected into the rat subarachnoid cavity, while the neural stem cells group was inject- ed with non-transfected neural stem cells. Dulbecco＇s modified Eagle＇s medium/F12 medium was injected into the rats in the spinal cord injury group as a control. At 1-4 weeks post injury, the motor function in the rat lower limbs was best in the human erythropoietin-neural stem ceils group, followed by the neural stem cells group, and lastly the spinal cord injury group. At 72 hours, compared with the spinal cord injury group, the apoptotic index and Caspase-3 gene and protein expressions were apparently decreased, and the bd-2 gene and protein expressions were noticeably increased, in the tissues surrounding the injured region in the human erythro- poietin-neural stem cells group. At 4 weeks, the somatosensory evoked potential latencies were cavities were clearly smaller and the motor and remarkably shorter in the human erythropoi- etin-neural stem cells group and neural stem cells group than those in the spinal cord injury group. These differences were particularly obvious in the human erythropoietin-neural stem cells group. More CM-Dil-positive cells and horseradish peroxidase-positive nerve fibers and larger amplitude motor and somatosensory evoked potentials were found in the human erythro- poietin-neural stem cells group and neural stem cells group than in the spinal cord injury group. Again, these differences were particularly obvious in the human erythropoietin-neural stem cells group. These data indicate that transplantation of erythropoietin gene-modified neural stem cells into the subarachnoid cavity to help repair spinal cord inj

关键词： nerve regeneration spinal cord injury neural stem cells erythropoietin motor function subarachnoid cavity transplantation injury recovery neural regeneration

Effect of exogenous spastin combined with polyethylene glycol on sciatic nerve injury

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Neural Regeneration Research 2019年第7期14卷 1271-1279页

作者： Yao-Fa Lin Zheng Xie Jun Zhou Hui-Hao Chen Wan-Wan Shao Hao-Dong Lin Department of Orthopedics Changzheng Hospitalthe Second Military Medical University Department of Orthopedics the Second People's Hospital of Karamay

Polyethylene glycol can connect the distal and proximal ends of an injured nerve at the cellular level through axonal fusion to avoid Wallerian degeneration of the injured distal nerve and promote peripheral nerve regeneration.However,this method can only prevent Wallerian degeneration in 10% of axons because the cytoskeleton is not repaired in a timely fashion.Reconstruction of the cytoskeletal trunk and microtubule network has been suggested to be the key for improving the efficiency of axonal fusion.As a microtubule-severing protein,spastin has been used to enhance cytoskeletal reconstruction.Therefore,we hypothesized that spastin combined with polyethylene glycol can more effectively promote peripheral nerve regeneration.A total of 120 male Sprague-Dawley rats were randomly divided into sham,suture,polyethylene glycol,and polyethylene glycol + spastin groups.In suture group rats,only traditional nerve anastomosis of the end-to-end suture was performed after transection of the sciatic nerve.In polyethylene glycol and polyethylene glycol + spastin groups,50 μL of polyethylene glycol or 25 μL of polyethylene glycol + 25 μL of spastin,respectively,were injected immediately under the epineurium of the distal suture.Sensory fiber regeneration distance,which was used to assess early nerve regeneration at 1 week after surgery,was shortest in the suture group,followed by polyethylene glycol group and greatest in the polyethylene glycol + spastin group.Behavioral assessment of motor function recovery in rats showed that limb function was restored in polyethylene glycol and polyethylene glycol + spastin groups at 8 weeks after surgery.At 1,2,4 and 8 weeks after surgery,sciatic functional index values and percentages of gastrocnemius muscle wet weight were highest in the sham group,followed by polyethylene glycol + spastin and polyethylene glycol groups,and lowest in the suture group.Masson staining was utilized to assess the morphology of muscle tissue.Morphological changes in skeletal muscle were detectable in suture,p

关键词： nerve regeneration peripheral nerves Wallerian degeneration polyethylene glycol axonal fusion spastin peripheral nerve injuries Masson staining microtubule neural regeneration

Mitochondrial division inhibitor 1 protects cortical neurons from excitotoxicity:a mechanistic pathway

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Neural Regeneration Research 2018年第9期13卷 1552-1560页

作者： Kuai Zhou Hai-Yuan Yang Peng-Yu Tang Wei Liu Yong-Jun Luo Bin Lv Jian Yin Tao Jiang Jian Chen Wei-Hua Cai Jin Fan Department of Orthopedics First Affiliated Hospital of Nanjing Medical University Department of Orthopedics Ben Q Hospital Affiliated to Nanjing Medical University Department of Orthopedics Affiliated Jiangning Hospital of Nanjing Medical University

Mitochondrial division inhibitor 1（Mdivi-1） is a selective cell-permeable inhibitor of dynamin-related protein-1（Drp1） and mitochondrial division.To investigate the effect of Mdivi-1 on cells treated with glutamate,cerebral cortex neurons isolated from neonatal rats were treated with 10 m M glutamate for 24 hours.Normal cultured cells and dimethyl sulfoxide-cultured cells were considered as controls.Apoptotic cells were detected by flow cytometry.Changes in mitochondrial morphology were examined by electron microscopy.Drp1,Bax,and casp ase-3 expression was evaluated by western blot assays and immunocytochemistry.Mitochondrial membrane potential was detected using the JC-1 probe.Twenty-four hours after 10 m M glutamate treatment,Drp1,Bax and caspase-3 expression was upregulated,Drp1 and Bax were translocated to mitochondria,mitochondrial membrane potential was decreased and the rate of apoptosis was increased.These effects were inhibited by treatment with 50 μM Mdivi-1 for 2 hours.This finding indicates that Mdivi-1 is a candidate neuroprotective drug that can potentially mitigate against neuronal injury caused by glutamate-induced excitotoxicity.

关键词： nerve regeneration mitochondrial division inhibitor 1 neurons apoptosis mitochondria division dynamin-related protein-I phospho-dynamin-related protein-1 Bax glutamate colocalization neural regeneration

Neuroprotective effects of electroacupuncture on early- and late-stage spinal cord injury

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Neural Regeneration Research 2015年第10期10卷 1628-1634页

作者： Min-fei Wu Shu-quan Zhang Jia-bei Liu Ye Li Qing-san Zhu Rui Gu Department of Orthopedics Bethune Second Hospital of Jilin University Department of Orthopedics Tianjin Nankai Hospital Department of Orthopedics China-Japan Union Hospital Jilin University

Previous studies have shown that the neurite growth inhibitor Nogo-A can cause secondary neural damage by activating Rho A. In the present study, we hypothesized that electroacupuncture promotes neurological functional recovery after spinal cord injury by inhibiting Rho A expression. We established a rat model of acute spinal cord injury using a modification of Allen＇s method. The rats were given electroacupuncture treatment at Dazhui（Du14）, Mingmen（Du4）, Sanyinjiao（SP6）, Huantiao（GB30）, Zusanli（ST36） and Kunlun（BL60） acupoints with a sparsedense wave at a frequency of 4 Hz for 30 minutes, once a day, for a total of 7 days. Seven days after injury, the Basso, Beattie and Bresnahan（BBB） locomotor scale and inclined plane test scores were significantly increased, the number of apoptotic cells in the spinal cord tissue was significantly reduced, and Rho A and Nogo-A m RNA and protein expression levels were decreased in rats given electroacupuncture compared with rats not given electroacupuncture. Four weeks after injury, pathological tissue damage in the spinal cord at the site of injury was alleviated, the numbers of glial fibrillary acidic protein- and neurofilament 200-positive fibers were increased, the latencies of somatosensory-evoked and motor-evoked potentials were shortened, and their amplitudes were increased in rats given electroacupuncture. These findings suggest that electroacupuncture treatment reduces neuronal apoptosis and decreases Rho A and Nogo-A m RNA and protein expression at the site of spinal cord injury, thereby promoting tissue repair and neurological functional recovery.

关键词： nerve regeneration spinal cord injury electroacupuncture locomotion Rho A Nogo-A glial fibrillary acidic protein neurofilament 200 neural regeneration

Internal fixator vs external fixator in the management of unstable pelvic ring injuries:A prospective comparative cohort study

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World Journal of orthopedics 2023年第7期14卷 562-571页

作者： Mohamed Abo-Elsoud Mostafa I Awad Mahmoud Abdel Karim Sherif Khaled Mohamed Abdelmoneim Department of Orthopedics and Traumatology Cairo University HospitalsCairo 11562Egypt department of Trauma and orthopedics Mataria Teaching HospitalCairo 4540046Egypt

BACKGROUND Reconstruction of the pelvic ring anatomy in unstable anterior pelvic ring injuries is a significant step to reduce the mortality rate associated with these injuries efficiently.There is a debate on using either an anterior subcutaneous pelvis internal fixator(INFIX)or an anterior supra-acetabular external fixator(EXFIX)to manage an unstable anterior pelvic ring fracture.AIM To compare the functional and radiological outcomes and complications of INFIX vs EXFIX in managing unstable pelvic ring injuries.METHODS A prospective cohort study included 54 patients with unstable pelvic ring fractures.The patients were divided into two groups;the INFIX group,in which 30 cases were fixed by INFIX,and the EXFIX group,in which 24 patients were treated by EXFIX.The average age in the EXFIX group was 31.17 years(16-57 years),while in the INFIX group,it was 34.5 years(17-53 years).The study included 20(66.7%)males and 10(33.3%)females in the INFIX group and 10(41.7%)males and 14(58.3%)females in the EXFIX group.The radiological outcomes were evaluated using Matta and Tornetta's score,and the functional outcomes using the Majeed score.RESULTS The results revealed a statistically significant difference between both groups(P=0.013)regarding radiological outcomes,according to Matta and Tornetta's score in favor of the INFIX group.Sitting,standing,and walking abilities were measured at a 3-mo follow-up visit using Majeed score modules.It was significantly better among the INFIX group than the EXFIX group in all three modules.At the final follow-up,both groups had no statistically significant difference according to the Majeed score;92.35 in the INFIX group and 90.99 in the EXFIX group(P=0.513).A lower surgical site infection rate was noticed in the INFIX group(P=0.007).CONCLUSION Anterior subcutaneous pelvis INFIX is associated with better radiological outcomes and a lower infection rate than anterior supra-acetabular EXFIX in managing patients with unstable anterior pelvic ring fractures.

关键词： Internal fixator External fixator Unstable Anterior Pelvic Injuries

A morphological study of age-related changes in medullary characteristics of proximal humerus

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Chinese Medical Journal 2022年第3期135卷 359-361页

作者： Wei Zhang Zuhao Chang Jiantao Li Peifu Tang Hua Chen Department of Orthopedics Chinese PLA General HospitalBeijing 100853China

To the Editor:Proximal humeral fracture(PHF)predominantly occurs in patients older than 60 years old with severe osteoporosis.[1]Although a majority of PHFs can be treated non-operatively,the complicated ones require surgical fixation.[2]In older individuals,the loss of trabecular structure and the calcar region in the proximal humeral medullary cavity makes them prone to comminuted fracture and loss of medial hinge support,leading to a high rate of implant failure and reoperation.[3]Recent studies have shown that endosteal augments incorporated into the locking plate construct might provide better medullary support and mechanical stability.[1]However,the endosteal augments used in PHF fixation are of different shapes,modes,and positions,which can lead to implant failure and reduction loss.[1,4,5]This may be because of a lack of understanding of the morphological changes that take place in the proximal humerus at different ages.Therefore,in this study,we analyzed and compared the anatomical degeneration pattern of the medullary canal between older and younger patients to have a better understanding of the medullary morphology of proximal humerus anatomically and the application of endosteal support clinically.

关键词： stability. fracture younger