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Progression in translational research on spinal cord injury based on microenvironment imbalance

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Bone Research 2022年第2期10卷 227-252页

作者： Baoyou Fan Zhijian Wei Shiqing Feng Department of Orthopedics Tianjin Medical University General HospitalInternational Science and Technology Cooperation Base of Spinal Cord InjuryTianjin Key Laboratory of Spine and Spinal Cord Injury154 Anshan RoadHeping DistrictTianjin 300052China Department of Orthopaedics Qilu HospitalShandong University Centre for OrthopaedicsCheeloo College of MedicineShandong UniversityJinanShandong 250012China

spinal cord injury(SCI) leads to loss of motor and sensory function below the injury level and imposes a considerable burden on patients, families, and society. repair of the injured spinal cord has been recognized as a global medical challenge for many *** progress has been made in research on the pathological mechanism of spinal cord injury. In particular, with the development of gene regulation, cell sequencing, and cell tracing technologies, in-depth explorations of the SCI microenvironment have become more feasible. However, translational studies related to repair of the injured spinal cord have not yielded significant results. This review summarizes the latest research progress on two aspects of SCI pathology: intraneuronal microenvironment imbalance and regenerative microenvironment imbalance. We also review repair strategies for the injured spinal cord based on microenvironment imbalance, including medications, cell transplantation, exosomes, tissue engineering, cell reprogramming, and rehabilitation. The current state of translational research on SCI and future directions are also discussed. The development of a combined, precise, and multitemporal strategy for repairing the injured spinal cord is a potential future direction.

关键词： translational injury precise

Ferroptosis inhibition protects vascular endothelial cells and maintains integrity of the blood-spinal cord barrier after spinal cord injury

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Neural regeneration Research 2023年第11期18卷 2474-2481页

作者： Wenxiang Li Xiaoqing Zhao Rong Zhang Xinjie Liu Zhangyang Qi Yang Zhang Weiqi Yang Yilin Pang Chenxi Zhao Baoyou Fan Ning Ran Jiawei Zhang Xiaohong Kong Shiqing Feng Xue Yao Shandong University Center for Orthopedics Department of OrthopedicsQilu Hospital of Shandong UniversityCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Tianjin key laboratory of spine and spinal cord National Spinal Cord Injury International Cooperation BaseDepartment of OrthopedicsTianjin Medical University General HospitalTianjinChina

Maintaining the integrity of the blood-spinal cord barrier is critical for the recove ry of spinal cord *** ptosis contributes to the pathogenesis of spinal cord *** hypothesized that ferroptosis is involved in disruption of the blood-s pinal cord *** this study,we administe red the ferroptosis inhibitor liproxstatin-1 intraperitoneally after contusive spinal co rd injury in ***-1 improved locomotor recovery and somatosensory evoked potential electrophysiological performance after spinal cord inju ***-1 maintained blood-spinal cord barrier integrity by upregulation of the expression of tight junction ***-1 inhibited ferroptosis of endothelial cell after spinal cord injury,as shown by the immunofluorescence of an endothelial cell marker(rat endothelium cell antigen-1,RECA-1) and fe rroptosis markers Acyl-CoA synthetase long-chain family member 4 and ***-1reduced brain endothelial cell ferroptosis in vitro by upregulating glutathione peroxidase 4 and downregulating Acyl-CoA synthetase long-chain family member4 and ***,inflammatory cell recruitment and astrogliosis were mitigated after liproxstatin-1 *** summary,liproxstatin-1im proved spinal cord injury recovery by inhibiting ferroptosis in endothelial cells and maintaining blood-s pinal co rd barrier integrity.

关键词： blood-spinal cord barrier ferroptosis liproxstatin-1 neuroinflammation spinal cord injury vascular endothelial cells

Engineering neuroregenerative microenvironment via aligned hydrogel-assisted magnetic stimulation for complete spinal cord injury repair

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Engineered regeneration 2024年第2期5卷 139-152页

作者： Chun-Yi Yang Zhe Meng Zhijun He Pengchao Ma Zhaohui Hou Kunkoo Kim Jingsong Lu Kaiyuan Yang Guihuai Wang Xiumei Wang State key laboratory of New Ceramics and Fine Processing Key Laboratory of Advanced Materials of Ministry of EducationSchool of Materials Science and EngineeringTsinghua UniversityBeijing 100084China Department of Neurosurgery Beijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijing102218China

Utilizing biomaterials in tissue engineering has shown considerable promise for tissue regeneration,particularly through delivering multimodel cell-regulatory signals,including the material-related signals and extrinsic *** this research,we developed a magnetic-responsive aligned nanofiber fibrin hydrogel(MAFG),integrating the structured alignment of nanofibers and the pliability of fibrin hydrogel with an external magnetic *** design aimed to enhance the regenerative response in spinal cord injury treatment.A medium-strength magnetic field,aligned with the spinal cord,was applied to aid motor function recovery in rats with spinal cord *** use of MAFG in this context not only intensified the effect of the magnetic field but also encouraged the activation and differentiation of native neural stem ***,this method effectively steered macrophage polarization towards a beneficial M2 phenotype,addressing immune dysregulation at the injury *** parallel application of magnetic field stimulation through MAFG in a spinal cord injury model contributed to the concurrent promotion of neurogenesis,angiogenesis,and immunomodulation,resulting in marked improvement in motor function in *** investigation underscores the therapeutic potential of magnetic field stimulation and highlights how aligning this stimulation with the spinal cord can significantly enhance the regenerative milieu at the injury site.

关键词： Angiogenesis Neurogenesis Immunomodulation Magnetic-responsive hydrogel Magnetic stimulation

Bioinformatics analysis of ferroptosis in spinal cord injury

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Neural regeneration Research 2023年第3期18卷 626-633页

作者： Jin-Ze Li Bao-You Fan Tao Sun Xiao-Xiong Wang Jun-Jin Li Jian-Ping Zhang Guang-Jin Gu Wen-Yuan Shen De-Rong Liu Zhi-Jian Wei Shi-Qing Feng International Cooperation Base of spinal cord injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryDepartment of OrthopedicsTianjin Medical University General HospitalTianjinChina Department of Orthopedics Qilu Hospital of Shandong UniversityJinanShandong ProvinceChina Shandong University Centre for Orthopedics Advanced Medical Research InstituteCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina

Ferroptosis plays a key role in aggravating the progression of spinal cord injury(SCI),but the specific mechanism remains *** this study,we constructed a rat model of T10 SCI using a modified Allen *** identified 48,44,and 27 ferroptosis genes that were differentially expressed at 1,3,and 7 days after SCI *** with the sham group and other SCI subgroups,the subgroup at 1 day after SCI showed increased expression of the ferroptosis marker acyl-CoA synthetase long-chain family member 4 and the oxidative stress marker malondialdehyde in the injured spinal cord while glutathione in the injured spinal cord was *** findings with our bioinformatics results suggested that 1 day after SCI was the important period of ferroptosis *** analysis identified the following top ten hub ferroptosis genes in the subgroup at 1 day after SCI:STAT3,JUN,TLR4,ATF3,HMOX1,MAPK1,MAPK9,PTGS2,VEGFA,and ***-time polymerase chain reaction on rat spinal cord tissue confirmed that STAT3,JUN,TLR4,ATF3,HMOX1,PTGS2,and RELA mRNA levels were up-regulated and VEGFA,MAPK1 and MAPK9 mRNA levels were *** potential compounds were predicted using the DSigDB database as potential drugs or molecules targeting ferroptosis to repair *** also constructed a ferroptosis-related mRNA-miRNA-lncRNA network in SCI that included 66 lncRNAs,10 miRNAs,and 12 *** results help further the understanding of the mechanism underlying ferroptosis in SCI.

关键词： bioinformatics drug ferroptosis Gene Ontology enrichment analysis gene-miRNA network Kyoto Encyclopedia of Genes and Genomes pathway mRNA-miRNA-lncRNA network progression spinal cord injury

Identification of key genes involved in recovery from spinal cord injury in adult zebrafish

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Neural regeneration Research 2022年第6期17卷 1334-1342页

作者： Wen-Yuan Shen Xuan-Hao Fu Jun Cai Wen-Chang Li Bao-You Fan Yi-Lin Pang Chen-Xi Zhao Muhtidir Abula Xiao-Hong Kong Xue Yao Shi-Qing Feng International Science and Technology Cooperation Base of spinal cord injury Tianjin Key Laboratory of Spine and Spinal CordDepartment of OrthopedicsTianjin Medical University General HospitalTianjinChina Tianjin Medicine and Health Research Center Tianjin Institute of Medical&Pharmaceutical SciencesTianjinChina School of Medicine Nankai UniversityTianjinChina

Zebrafish are an effective vertebrate model to study the mechanisms underlying recovery after spinal cord *** subacute phase after spinal cord injury is critical to the recovery of neurological function,which involves tissue bridging and axon *** this study,we found that zebrafish spontaneously recovered 44%of their swimming ability within the subacute phase(2 weeks)after spinal cord *** this period,we identified 7762 differentially expressed genes in spinal cord tissue:2950 were up-regulated and 4812 were *** differentially expressed genes were primarily concentrated in the biological processes of the respiratory chain,axon regeneration,and cell-component *** genes were also mostly involved in the regulation of metabolic pathways,the cell cycle,and gene-regulation *** verified the gene expression of two differentially expressed genes,clasp2 up-regulation and h1m down-regulation,in zebrafish spinal cord tissue in *** enrichment analysis revealed that up-regulated clasp2 functions similarly to microtubule-associated protein,which is responsible for axon extension regulated by ***-regulated h1m controls endogenous stem cell differentiation after spinal cord *** study provides new candidate genes,clasp2 and h1m,as potential therapeutic intervention targets for spinal cord injury repair by *** experimental procedures and protocols were approved by the Animal Ethics Committee of Tianjin Institute of Medical&Pharmaceutical Sciences(approval ***-EAEP-Q-2019-02)on September 24,2019.

关键词： axon regeneration clasp2 endogenous neural stem cells h1m microtubule nanog neural regeneration neurogenesis spinal cord injury subacute phase

Multimodal treatment for spinal cord injury: a sword of neuroregeneration upon neuromodulation

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Neural regeneration Research 2020年第8期15卷 1437-1450页

作者： Ya Zheng Ye-Ran Mao Ti-Fei Yuan Dong-Sheng Xu Li-Ming Cheng Rehabilitation Section Spine Surgery Division of Department of OrthopedicsTongji Hospital Affiliated to Tongji University School of MedicineShanghaiChina Shanghai key laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina key laboratory of spine and spinal cord injury repair and regeneration of Ministry of Education of the People’s Republic of China Tongji UniversityShanghaiChina spine Surgery Division of Department of Orthopedics Tongji Hospital Affiliated to Tongji University School of MedicineShanghaiChina

spinal cord injury is linked to the interruption of neural pathways,which results in irreversible neural *** repair and neuroregeneration are critical goals and issues for rehabilitation in spinal cord injury,which require neural stem cell repair and multimodal neuromodulation techniques involving personalized rehabilitation *** the involvement of endogenous stem cells in neurogenesis and neural repair,exogenous neural stem cell transplantation is an emerging effective method for repairing and replacing damaged tissues in central nervous system ***,to ensure that endogenous or exogenous neural stem cells truly participate in neural repair following spinal cord injury,appropriate interventional measures(e.g.,neuromodulation)should be *** techniques,such as noninvasive magnetic stimulation and electrical stimulation,have been safely applied in many neuropsychiatric *** is increasing evidence to suggest that neuromagnetic/electrical modulation promotes neuroregeneration and neural repair by affecting signaling in the nervous system;namely,by exciting,inhibiting,or regulating neuronal and neural network activities to improve motor function and motor learning following spinal cord *** studies have indicated that fine motor skill rehabilitation training makes use of residual nerve fibers for collateral growth,encourages the formation of new synaptic connections to promote neural plasticity,and improves motor function recovery in patients with spinal cord *** the development of biomaterial technology and biomechanical engineering,several emerging treatments have been developed,such as robots,brain-computer interfaces,and *** treatments have the potential to help millions of patients suffering from motor dysfunction caused by spinal cord ***,large-scale clinical trials need to be conducted to validate their *** review evaluated the efficacy of ne

关键词： brain-computer interface technology multimodal rehabilitation nerve regeneration neural circuit reconstruction neural regeneration neuromodulation rehabilitation training spinal cord injury stem cells transcranial direct current stimulation transcranial magnetic stimulation

Anisotropic microtopography surface of chitosan scaffold regulating skin precursor-derived Schwann cells towards repair phenotype promotes neural regeneration

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Regenerative Biomaterials 2024年第3期3卷 68-81页

作者： Meng Cong Xia Wu Lingjie Zhu Guohao Gu Fei Ding Guicai Li Haiyan Shi key laboratory of Neuroregenration of jiangsu and Ministry of Education and Co-Innovation Center of Neuroregeneration Nantong UniversityNantong 226001China Department of Pathophysiology School of MedicineNantong UniversityNantong 226001China

For repairing peripheral nerve and spinal cord defects,biomaterial scaffoid-based cell-therapy was emerged as an effective strategy,requiring the positive response of seed cells to biomaterial substrate and environment *** work highlighted that the imposed surface properties of scaffold could provide important guidance cues to adhered cells for ***,the insufficiency of native Schwann cells and unclear cellular response mechanisms remained to be *** that,this study aimed to illuminate the micropatterned chitosan-film action on the rat skin precursor-derived Schwann cells(SKP-SCs).Chitosanfilm with different ridge/groove size was fabricated and applied for the SKP-SCs *** indicated that SKP-SCs cultured on 30μm size microgroove surface showed better oriented alignment *** SKP-sCs presented similar genic phenotype as repair Schwann cells,increasing expression of c-Jun,neural cell adhesion molecule,and neurotrophic receptor ***,SKP-SC-secretome was subjected to cytokine array GS67 assay,data indicated the regulation of paracrine phenotype,a panel of cytokines was verifed up-regulated at secreted level and gene expression level in induced *** up-regulated cytokines exhibit a series of promotive neural regeneration functions,including cell survival,cell migration,cell proliferation,angiogenesis,axon growth,and cellular organization *** bioinformatics ***,the effectively polarized SKP-SCs-sourced secretome,promoted the proliferation and migration capacity of the primarily cultured native rat Schwann cells,and augmented neurites growth of the cultured motoneurons,as well as boosted axonal regrowth of the axotomy-injured *** together,SKP-SCs obtained pro-neuroregeneration phenotype in adaptive response to the anisotropic topography surface of chitosan-film,displayed the oriented parallel growth,the transition towards repair Schwann cell genic phenot

关键词： anisotropic microtopography skin precursor-derived Schwann cells chitosan-flm neural regeneration phenotype regulation

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Genomics, Proteomics & Bioinformatics 2022年第5期20卷 1028-1036页

作者： Zhiting Wei Sheng Zhu Xiaohan Chen Chenyu Zhu Bin Duan Qi Liu Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China key laboratory of spine and spinal cord injury repair and regeneration(Tongji University) Ministry of EducationOrthopaedic Department of Tongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Shanghai Research Institute for Intelligent Autonomous Systems Shanghai 201210China

Transcriptional phenotypic drug discovery has achieved great success,and various compound perturbation-based data resources,such as connectivity map(CMap)and library of integrated network-based cellular signatures(LINCS),have been *** strategies fully mining these resources for phenotypic drug discovery have been *** them,the fundamental issue is to define the proper similarity between transcriptional ***,such similarity has been defined in an unsupervised ***,due to the high dimensionality and the existence of high noise in high-throughput data,similarity defined in the traditional way lacks robustness and has limited *** this end,we present Dr Sim,which is a learning-based framework that automatically infers similarity rather than defining *** evaluated Dr Sim on publicly available in vitro and in vivo datasets in drug annotation and *** results indicated that Dr Sim outperforms the existing *** conclusion,by learning transcriptional similarity,Dr Sim facilitates the broad utility of high-throughput transcriptional perturbation data for phenotypic drug *** source code and manual of Dr Sim are available at https://***/bm2-lab/Dr Sim/.

关键词： Metric learning Transcriptional profile similarity Drug annotation Drug repositioning LINCS

Effects of cortical intermittent theta burst stimulation combined with precise root stimulation on motor function after spinal cord injury: a case series study

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Neural regeneration Research 2022年第8期17卷 1821-1826页

作者： Ye-Ran Mao Zhong-Xia Jin Ya Zheng Jian Fan Li-Juan Zhao Wei Xu Xiao Hu Chun-Ya Gu Wei-Wei Lu Guang-Yue Zhu Yu-Hui Chen Li-Ming Cheng Dong-Sheng Xu Department of Rehabilitation Baoshan BranchShuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina Institute of Rehabilitation Medicine Shanghai University of Traditional Chinese MedicineShanghaiChina Department of spinal cord injury Rehabilitation Shanghai Yangzhi Rehabilitation HospitalShanghai Sunshine Rehabilitation CenterTongji University School of MedicineShanghaiChina spine Surgery Division of Department of Orthopedics Tongji Hospital Affiliated to Tongji University School of MedicineShanghaiChina Surgery Division of Department of Orthopedics Tongji Hospital Affiliated to Tongji University School of MedicineShanghaiChina key laboratory of spine and spinal cord injury repair and regeneration Ministry of EducationShanghaiChina Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation Ministry of EducationShanghaiChina

Activation and reconstruction of the spinal cord circuitry is important for improving motor function following spinal cord *** conducted a case series study to investigate motor function improvement in 14 patients with chronic spinal cord injury treated with 4 weeks of unilateral(right only)cortical intermittent theta burst stimulation combined with bilateral magnetic stimulation of L3-L4 nerve roots,five times a *** resting motor evoked potential amplitude was increased,central motor conduction time on the side receiving cortical stimulation was significantly decreased,and lower extremity motor score,Berg balance score,spinal cord independence measure-III score,and 10 m-walking speed were all increased after *** resting motor evoked potential amplitude was positively correlated with lower extremity motor score after 4 weeks of *** findings suggest that cortical intermittent theta burst stimulation combined with precise root stimulation can improve nerve conduction of the corticospinal tract and lower limb motor function recovery in patients with chronic spinal cord injury.

关键词： central motor conduction time intermittent theta burst lower extremity motor score motor evoked potential stimulation neuromodulation neuronal plasticity spinal cord injury transcranial magnetic stimulation