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Peripheral nerve regeneration through nerve conduits evokes differential expression of growth-associated protein-43 in the spinal cord

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Neural Regeneration Research 2023年第8期18卷 1852-1856页

作者： Jesús Chato-Astrain Olga Roda David Sánchez-Porras Esther Miralles Miguel Alaminos Fernando Campos Óscar Darío García-García Víctor Carriel Department of Histology(Tissue Engineering Group) University of GranadaInstituto de Investigación Biosanitaria ibs.GRANADAGranadaSpain Department of Human Anatomy and Embryology University of GranadaGranadaSpain Unit of Clinical Neurophysiology University Hospital San CecilioGranadaSpain

Growth-associated protein 43 plays a key role in neurite outgrowth through cytoskeleton *** have previously demonstrated that structural damage of peripheral nerves induces growth-associated protein 43 upregulation to promote growth cone ***,the limited regenerative capacity of the central nervous system due to an inhibitory environment prevents major changes in neurite outgrowth and should be presumably associated with low levels of growth-associated protein 43 ***,central alterations due to peripheral nerve damage have never been assessed using the growthassociated protein 43 *** this study,we used the tubulization technique to repair 1 cm-long nerve gaps in the rat nerve injury/repair model and detected growth-associated protein 43 expression in the peripheral and central nervous ***,histological analysis of the regeneration process confirmed an active regeneration process of the nerve gaps through the conduit from 10 days *** growth-associated protein 43 expression profile varied across regions and follow-up times,from a localized expression to an abundant and consistent expression throughout the regeneration tissue,confirming the presence of an active nerve regeneration ***,spinal cord changes were also histologically assessed,and no apparent changes in the structural and cellular organization were observed using routine staining ***,remarkable differences and local changes appeared in growth-associated protein 43 expression at the spinal cord level,in particular at 20 days post-repair and ***-associated protein 43 protein was first localized in the gracile fasciculus and was homogeneously distributed in the left posterior *** findings differed from the growth-associated protein 43 pattern observed in the healthy control,which did not express growth-associated protein 43 at these *** results revealed a differential expression in growth-associate

关键词： growth-associated protein 43(GAP-43) immunohistochemistry nerve guide nerve tissue regeneration peripheral nerve repair spinal cord tissue engineering

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spinal cord Stimulation Enhances Microglial Activation in the spinal cord of Nerve-Injured Rats

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Neuroscience Bulletin 2020年第12期36卷 1441-1453页

作者： Bin Shu Shao-Qiu He Yun Guan Department of Anesthesiology and Critical Care Medicine School of MedicineJohns Hopkins UniversityBaltimoreMD 21205USA Present Address:Department of Anesthesiology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Neurological Surgery School of MedicineJohns Hopkins UniversityBaltimoreMD 21205USA

Microglia can modulate spinal nociceptive ***,their role in spinal cord stimulation(SCS)-induced pain inhibition is ***,we examined how SCS affects microglial activation in the lumbar cord of rats with chronic constriction injury(CCI)of the sciatic *** rats received conventional SCS(50 Hz,80%motor threshold,180 min,2 sessions/day)or sham stimulation on days 18-20 *** transiently attenuated the mechanical hypersensitivity in the ipsilateral hind paw and increased OX-42 immunoreactivity in the bilateral dorsal *** also upregulated the mRNAs of Ml-like markers,but not M2-like *** NOS protein expression was increased,but brain-derived neurotrophic factor was decreased after *** minocycline(1μg-100μg),which inhibits microglial activation,dosedependently attenuated the mechanical *** with low-dose minocycline(1μg,30 min)prolonged the SCS-induced pain *** findings suggest that conventional SCS may paradoxically increase spinal M1-like microglial activity and thereby compromise its own ability to inhibit pain.

关键词： spinal cord stimulation Microglia Neuropathic pain spinal cord Rat

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spinal cord biological safety of image-guided radiation therapy versus conventional radiation therapy

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Neural Regeneration Research 2012年第35期7卷 2755-2760页

作者： Wanlong Xu Xilinbaoleri Hao Liu Ruozheng Wang Jingping Bai The Affiliated Tumor Hospital of Xinjiang Medical University People's Hospital of Xinjiang Uygur Autonomous Region

Tumor models were simulated in purebred Beagles at the T9-10 levels of the spinal cord and treated with spinal image-guided radiation therapy or conventional radiation therapy with 50 or 70 Gy total radiation. Three months after radiation, neuronal injury at the T9-10 levels was observed, including reversible injury induced by spinal image-guided radiation therapy and apoptosis induced by conventional radiation therapy. The number of apoptotic cells and expression of the proapoptotic protein Fas were significantly reduced, but expression of the anti-apoptotic protein heat shock protein 70 was significantly increased after image-guided radiation therapy compared with the conventional method of the same radiation dose. Moreover, the spinal cord cell apoptotic index positively correlated with the ratio of Fas/heat shock protein 70. These findings indicate that 3 months of radiation therapy can induce a late response in the spinal cord to radiation therapy; image-guided radiation therapy is safer and results in less neuronal injury compared with conventional radiation therapy.

关键词： Image-guided radiation therapy conventional radiation therapy spinal cord neurons apoptosis Fas heat shock protein 70 biological safety vertebral body tumor

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GABAA receptor partially mediated propofol-induced hyperalgesia at superspinal level and analgesia at spinal cord level in rats

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Acta Pharmacologica Sinica 2004年第12期25卷 53-59页

作者： Qin-yun WANG2,3, Jun-li CAO2, Yin-ming ZENG2, Ti-jun DAI2,4 2Jiangsu Institute of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou, 221002, China 3Department of Anesthesiology, the1st Affiliated Hospitalof Soochow University, Suzhou 215006, China 江苏省麻醉学研究所江苏省麻醉学重点实验室 Xuzhou 221002

AIM: To observe effects of propofol on nociceptive response at superspinal and spinal level in rats. METHODS: Two hundreds and fifty-eight Sprague-Dawley male rats were randomized into thirty-two groups. Propofol and bicuculline were microinjected into lateral ventricle (icv), ventrolateral periaqueductal gray (vlPAG), intrathecal (ith), and intraperitoneal (ip). The noxious responses were evaluated by hot plate and formalin test. RESULTS: In hot-plate test, systemic and superspinal administration of propofol (40 mg·kg-1 ip, 100 μg in 10 μL, icv, and 4 μg in 0.4 μL vlPAG microinjection) produced hyperalgesia (Pspinal administration of propofol (40 mg·kg-1 ip, 4 μg in 0.4 μL, vlPAG) also produced hyperal- gesia (Pspinal and analgesia at spinal cord in rats.

关键词： GABA receptors propofol pain ventrolateral periaqueductal gray spinal cord

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Human adipose tissue-and umbilical cord-derived stem cells: which is a better alternative to treat spinal cord injury?

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Neural Regeneration Research 2020年第12期15卷 2306-2317页

作者： Ai-Mei Liu Bo-Li Chen Ling-Tai Yu Tao Liu Ling-Ling Shi Pan-Pan Yu Yi-Bo Qu Kwok-Fai So Li-Bing Zhou Guangdong-Hongkong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Guangzhou Regenerative Medicine and Health Guangdong Laboratory GuangzhouGuangdong ProvinceChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina

Multiple types of stem cells have been proposed for the treatment of spinal cord injury,but their comparative information remains *** this study,a rat model of T10 contusion spinal cord injury was established by the impactor *** umbilical cord-derived mesenchymal stem cells(UCMSCs)or human adipose tissue-derived mesenchymal stem cells(ADMSCs)(2.5μL/injection site,1×10^5 cells/μL)was injected on rostral and caudal of the injury segment on the ninth day after *** injected with mesenchymal stem cell culture medium were used as *** results show that although transplanted UCMSCs and ADMSCs failed to differentiate into neurons or glial cells in vivo,both significantly improved motor and sensory *** spinal cord injury,UCMSCs and ADMSCs similarly promoted spinal neuron survival and axonal regeneration,decreased glial scar and lesion cavity formation,and reduced numbers of active *** analysis of spinal samples showed a specific increase of interleukin-10 and decrease of tumor necrosis factorαin the ADMSC group,as well as a downregulation of macrophage inflammatory protein 3αin both UCMSC and ADMSC groups at 3 days after cell *** of interleukin-10 and interleukin-13 was observed in both UCMSC and ADMSC groups at 7 days after cell *** tagging for relative and absolute quantitation proteomics analyses showed that UCMSCs and ADMSCs induced changes of multiple genes related to axonal regeneration,neurotrophy,and cell apoptosis in common and specific *** conclusion,UCMSC and ADMSC transplants yielded quite similar contributions to motor and sensory recovery after spinal cord injury via anti-inflammation and improved axonal ***,there were some differences in cytokine and gene expression induced by these two types of transplanted *** experiments were approved by the Laboratory Animal Ethics Committee at Jinan University(approval No.20180228026)on Febru

关键词： behavior central nervous system factor inflammation model spinal cord stem cells transplantation

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Fetal cell microchimerism in the maternal mouse spinal cord

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Neuroscience Bulletin 2014年第1期30卷 81-89页

作者： Guohui Zhang Yunan Zhao Xin-Min Li Jiming Kong Department of Forensic Medicine Hebei North University Department of Human Anatomy and Cell Science Faculty of Medicine University of Manitoba Department of Psychiatry University of Manitoba

Fetal cell microchimerism refers to the persistence of fetal cells in the maternal tissues following pregnancy. It has been detected in peripheral organs and the brain, but its existence in the spinal cord has not been reported. Our aim was to detect fetal cell microchimerism in the spinal cord of maternal mice. C57BL/6 female mice were crossed with GFP transgenic male mice and sacrificed after their first or third delivery. GFP-positive cells, which were presumably from fetuses whose fathers were GFP transgenic, were detected in the spinal cord by fluorescence microscopy and immunohistochemistry. PCR was also performed to detect GFP DNA, which must come from GFP hemizygous fetuses. We found GFP-positive cells and detectable GFP DNA in most of the maternal spinal cords. Twenty percent （1/5） of the mice that were only pregnant once had detectable fetal cells, while 80% （4/5） of those that were pregnant three times had detectable fetal cells. Some fetal cells, which not only emitted green fluorescence but also expressed NeuN, were detected in the spinal cords from maternal mice. These results indicate that fetal cells migrate into the spinal cord of a maternal mouse during and/or after the gestational period, and the fetal cells may differentiate into neurons in the spinal cord.

关键词： fetal cell microchimerism greenfluorescent protein spinal cord mouse

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Effectiveness of oral motor respiratory exercise and vocal intonation therapy on respiratory function and vocal quality in patients with spinal cord injury:a randomized controlled trial

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Neural Regeneration Research 2021年第2期16卷 375-381页

作者： Xiao-Ying Zhang Yi-Chuan Song Chang-Bin Liu Chuan Qin Song-Huai Liu Jian-Jun Li School of Rehabilitation Medicine Capital Medical UniversityBeijingChina China Rehabilitation Science Institute BeijingChina Beijing Key Laboratory of Neural Injury and Rehabilitation BeijingChina Center of Neural Injury and Repair Beijing Institute for Brain DisordersBeijingChina Music Therapy Center Department of PsychologyChina Rehabilitation Research CenterBeijingChina Department of Rehabilitation Medicine Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Department of spinal and Neural Functional Reconstruction China Rehabilitation Research CenterBeijingChina

Singing,as a method of combining respiratory function exercise and vocal intonation therapy,provides a new direction for respiratory function exercise in patients with spinal cord *** randomized controlled trial investigated the effects of oral motor respiratory exercise and vocal intonation therapy on respiratory function and vocal quality in patients with spinal cord *** 31 included patients with spinal cord injury,18 completed the *** 18 patients were randomly assigned to undergo music therapy(intervention group,30 min/d,5 times a week,for a total of 12 weeks;n=9,7 males and 2 females;30.33±11.74 years old)or normal respiratory training(control group,n=9;8 males and 1 female;34.78±11.13 years old).Both patient groups received routine treatment *** and at 6 and 12 weeks after intervention,a standard respiratory function test,a voice test,the ***'s Respiratory Questionnaire,and a quality of life questionnaire were *** results showed that the inspiratory capacity,forced expiratory volume in 1 second,forced vital capacity,maximal mid-expiratory flow rate,sing-loud pressure level,and sustained note length were significantly increased in the intervention group compared with the control *** ***'s Respiratory Questionnaire and quality of life results of patients in the intervention group were significantly superior to those in the control *** findings suggest that oral motor respiratory exercise and vocal intonation therapy,as respiratory training methods in music therapy,are effective and valuable for improving respiratory dysfunction and vocal quality in patients with spinal cord *** study was approved by the Ethics Committee of China Rehabilitation Research Center(approval No.2019-78-1)on May 27,2019 and was registered with the Chinese Clinical Trial Registry(registration number:Chi CTR1900026922)on October 26,2019.

关键词： central nervous system clinical trial injury oral motor randomized repair respiratory exercise spinal cord

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Upregulation of Chemokine CXCL12 in the Dorsal Root Ganglia and spinal cord Contributes to the Development and Maintenance of Neuropathic Pain Following Spared Nerve Injury in Rats

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Neuroscience Bulletin 2016年第1期32卷 27-40页

作者： Liying Bai Xinru Wang Zhisong Li Cunlong Kong Yonghui Zhao Jun-Liang Qian Quancheng Kan Wei Zhang Ji-Tian Xu Department of Physiology and Neurobiology Zhengzhou University School of Medicine Department of Anesthesiology The First Affiliated HospitalZhengzhou University Department of Pharmacy The First Affiliated HospitalZhengzhou University

Emerging evidence indicates that CXCL12/ CXCR4 signaling is involved in chronic pain. However, few studies have systemically assessed its role in direct nerve injury-induced neuropathic pain and the underlying mech- anism. Here, we determined that spared nerve injury （SNI） increased the expression of CXCL12 and its cognate receptor CXCR4 in lumbar 5 dorsal root ganglia （DRG） neurons and satellite glial cells. SNI also induced long- lasting upregulation of CXCL12 and CXCR4 in the ipsi- lateral L4-5 spinal cord dorsal horn, characterized by CXCL12 expression in neurons and microglia, and CXCR4 expression in neurons and astrocytes. Moreover, SNI- induced a sustained increase in TNF-α expression in the DRG and spinal cord. Intraperitoneal injection （i.p.） of the TNF-α synthesis inhibitor thalidomide reduced the SNI-in- duced mechanical hypersensitivity and inhibited the expression of CXCL12 in the DRG and spinal cord. Intrathecal injection （i.t.） of the CXCR4 antagonist AMD3100, both 30 rain before and 7 days after SNI, reduced the behavioral signs of allodynia. Rats given an i.t. or i.p. bolus of AMD3100 on day 8 of SNI exhibited attenuated abnormal pain behaviors. The neuropathic pain established following SNI was also impaired by i.t. admin- istration of a CXCL12-neutralizing antibody. Moreover, repetitive i.t. AMD3100 administration prevented the acti- vation of ERK in the spinal cord. The mechanical hyper- sensitivity induced in nai＇ve rats by i.t. CXCL12 was alleviated by pretreatment with the MEK inhibitor PD98059. Collectively, our results revealed that TNF-α might mediate the upregulation of CXCL12 in the DRG and spinal cord following SNI, and that CXCL 12/CXCR4 sig- naling via ERK activation contributes to the development and maintenance of neuropathic pain.

关键词： Spared nerve injury CXCL12 TNF-α Neuropathic pain Extracellular signal-regulated kinase spinal cord

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Progress in clinical trials of cell transplantation for the treatment of spinal cord injury:how many questions remain unanswered?

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Neural Regeneration Research 2021年第3期16卷 405-413页

作者： Xu-Chang Hu Yu-Bao Lu Yong-Na Yang Xue-Wen Kang Yong-Gang Wang Bing Ma Shuai Xing Key Laboratory of Bone and Joint Diseases Research of Gansu Province Department of OrthopedicsLanzhou University Second HospitalLanzhouGansu ProvinceChina Second Clinical Medical College Lanzhou UniversityLanzhouGansu ProvinceChina Department of Neurology The First People’s Hospital of Lanzhou CityLanzhouGansu ProvinceChina

spinal cord injury can lead to severe motor,sensory and autonomic nervous ***,there is currently no effective treatment for spinal cord *** stem cells and progenitor cells,bone marrow mesenchymal stem cells,olfactory ensheathing cells,umbilical cord blood stem cells,adipose stem cells,hematopoietic stem cells,oligodendrocyte precursor cells,macrophages and Schwann cells have been studied as potential treatments for spinal cord *** treatments were mainly performed in ***,subtle changes in sensory function,nerve root movement and pain cannot be fully investigated with animal *** these cell types have shown excellent safety and effectiveness in various animal models,sufficient evidence of efficacy for clinical translation is still *** transplantation should be combined with tissue engineering scaffolds,local drug delivery systems,postoperative adjuvant therapy and physical rehabilitation training as part of a comprehensive treatment plan to provide the possibility for patients with SCI to return to normal *** review summarizes and analyzes the clinical trials of cell transplantation therapy in spinal cord injury,with the aim of providing a rational foundation for the development of clinical treatments for spinal cord injury.

关键词： central nervous system clinical trials injury plasticity protection regeneration repair spinal cord stem cells

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p75 neurotrophin receptor signal pathway influence on apoptosis in anterior horn neurons of the spinal cord in a rat model of cauda equina compression injury

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Neural Regeneration Research 2009年第12期4卷 979-985页

作者： Haopeng Li Jie Chen Xijing He Siyue Xu Yu Liu Department of Orthopaedics Second Affiliated Hospital College of Medicine Xi'an Jiaotong University Xi'an 710004 Shaanxi Province China

BACKGROUND： Studies have demonstrated that cauda equina compression results in apoptosis of motor neurons in the spinal cord. The combination of p75 neurotrophin receptor （p75NTR） and precursor of nerve growth factor （pro-NGF） expression initiates the apoptotic pathway and induces neuronal apoptosis. However, few reports have focused on the p75-mediated mechanism of neuronal apoptosis following cauda equine compression injury OBJECTIVE： To determine apoptosis of spinal cord neurons and activation of the pro-NGF-p75NTR-JNK（c-Jun N-terminal kinase） signal pathway in rats following cauda equina compression, and to verify experimental outcomes. DESIGN, TIME AND SETTING： A randomized, controlled, in vivo experiment was performed at the Medical Experimental Center of Xi＇an Jiaotong University between April and November in 2008. MATERIALS： Streptavidin-perosidase kit was purchased from Wuhan Boster, China; in situ end labeling detection kit was provided by Promega, USA; type AEG-220G electron microscope was purchased from Hitachi, Japan. METHODS： A total of 48 healthy, adult, female, Sprague Dawley rats were randomly assigned to three groups： normal （n = 6）, sham-surgery （n = 6）, and compression （n = 36）. The compression group was randomly assigned to six subsets at 1,3, 5, 7, 14, and 28 days, respectively, with 6 rats in each subset. A cylindrical silica gel stick was implanted into the rats to compress 75% of the vertebral canal in the compression group; in the sham-surgery group, only vertebral resection was performed; and no procedures were performed in the normal group. MAIN OUTCOME MEASURES： At 1,3, 5, 7, 14, and 28 days following compression, L2-3 spinal cord segments were processed for immunohistochemistry, in situ cell apoptosis detection, and transmission electron microscopy observation. Nissl staining was used to observe neuronal survival in the L2 spinal cord segment. Immunohistochemistry was applied to detect expressions of pro-NGF, p75NTR, and JNK in the L2 s

关键词： cauda equina syndrome p75 neurotrophin receptor spinal cord neurons apoptosis anterior horn

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