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Mutual regulation of microglia and astrocytes after Gas6 inhibits spinal cord injury

Neural Regeneration Research 2025年第2期20卷 557-573页

作者： Jiewen Chen Xiaolin Zeng Le Wang Wenwu Zhang Gang Li Xing Cheng Peiqiang Su Yong Wan Xiang Li department of Spine Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Guangdong Province Key Laboratory of orthopedics and traumatology GuangzhouGuangdong ProvinceChina

Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord *** and astrocytes play key roles in the spinal cord injury micro-environment and share a close ***,the mechanisms involved remain *** this study,we found that after spinal cord injury,resting microglia(M0)were polarized into pro-inflammatory phenotypes(MG1 and MG3),while resting astrocytes were polarized into reactive and scar-forming *** expression of growth arrest-specific 6(Gas6)and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord *** vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia,and even inhibited the cross-regulation between *** further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling ***,in turn,inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling *** vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord,thereby promoting tissue repair and motor function ***,Gas6 may play a role in the treatment of spinal cord *** can inhibit the inflammatory pathway of microglia and polarization of astrocytes,attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment,and thereby alleviate local inflammation and reduce scar formation in the spinal cord.

关键词： astrocytes Axl cell polarization Gas6 Hippo signal inflammatory micro-environment intercellular interaction microglia single-cell sequencing spinal cord injury

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Exosomes originating from neural stem cells undergoing necroptosis participate in cellular communication by inducing TSC2 upregulation of recipient cells following spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3273-3286页

作者： Shiming Li Jianfeng Li Guoliang Chen Tao Lin Penghui Zhang Kuileung Tong Ningning Chen Shaoyu Liu Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research Department of Orthopedic SurgeryThe Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdong ProvinceChina department of Orthopedic Surgery The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina department of orthopedics and traumatology Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina department of Orthopedic Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina department of Orthopedic Surgery The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord *** exosomes are recognized as playing a pivotal role in neural stem cells exocrine function,their precise function in spinal cord injury remains *** investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury,we conducted singlecell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord ***,we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted *** results showed that necroptosis did not significantly impact the fundamental characteristics or number of *** sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs,104 long non-coding RNAs,720 circular RNAs,and 14 microRNAs compared with the control *** of a competing endogenous RNA network identified the following hub genes:tuberous sclerosis 2(Tsc2),solute carrier family 16 member 3(Slc16a3),and forkhead box protein P1(Foxp1).Notably,a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord ***2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury ***,in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other *** assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling *** addition,Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling

关键词： cellular communication competing endogenous RNA exosomes Foxp1 necroptosis neural stem cells Slc16a3 spinal cord injury transcriptome sequencing Tsc2

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Jisuikang, a Chinese herbal formula, increases neurotrophic factor expression and promotes the recovery of neurological function after spinal cord injury

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Neural Regeneration Research 2017年第9期12卷 1519-1528页

作者： Yang Guo Yong Ma Ya-lan Pan Su-yang Zheng Jian-wei Wang Gui-cheng Huang Institute of traumatology & orthopedics and Laboratory of New Techniques of Restoration & Reconstruction of orthopedics and traumatology Nanjing University of Chinese Medicine department of traumatology & orthopedics Affiliated Hospital of Nanjing University of Chinese Medicine department of traumatology & orthopedics Wuxi Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine

The Chinese medicine compound, ]isuikang, can promote recovery of neurological function by inhibiting lipid peroxidation, scavenging oxygen free radicals, and effectively improving the local microenvironment after spinal cord injury. However, the mechanism remains unclear. Thus, we established a rat model of acute spinal cord injury using a modified version of Allen＇s method. Jisuikang （50, 25, and 12.5 g/kg/d） and prednis- olone were administered 30 minutes after anesthesia. Basso, Beattie, and Bresnahan locomotor scale scores and the oblique board test showed improved motor function recovery in the prednisone group and moderate-dose Jisuikang group compared with the other groups at 3-7 days post-injury. The rats in the moderate-dose Jisuikang group recovered best at 14 days post-injury. Hematoxylin-eosin staining and transmis- sion electron microscopy showed that the survival rate of neurons in treatment groups increased after 3-7 days of administration. Further, the structure of neurons and glial cells was more distinct, especially in prednisolone and moderate-dose Jisuikang groups. Western blot assay and immunohistochemistry showed that expression of brain-derived neurotrophic factor （BDNF） in injured segments was maintained at a high level after 7-14 days of treatment. In contrast, expression of nerve growth factor （NGF） was down-regulated at 7 days after spinal cord injury. Re- al-time fluorescence quantitative polymerase chain reaction showed that expression of BDNF and NGF mRNA was induced in injured segments by prednisolone and Jisuikang. At 3-7 days after injury, the effect of prednisolone was greater, while 14 days after injury, the effect of moder- ate-dose Jisuikang was greater. These results confirm that Jisuikang can upregulate BDNF and NGF expression for a prolonged period after spinal cord injury and promote repair of acute spinal cord injury, with its effect being similar to prednisolone.

关键词： nerve regeneration spinal cord injury Jisuikang Chinese medicine prednisolone microenvironment axon regeneration secondary changes neuronal apoptosis brain-derived neurotrophic factor nerve growth factor neural regeneration

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Factors that influence the results of indirect decompression employing oblique lumbar interbody fusion

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World Journal of orthopedics 2024年第8期15卷 734-743页

作者： Andrey E Bokov Svetlana Y Kalinina Mingiyan I Khaltyrov Alexandr P Saifullin Anatoliy A Bulkin department of neurosurgery Institute of Traumatology and OrthopedicsPrivolzhsky Research Medical UniversityNizhny Novgorod603005Russia department of traumatology Orthopedics and NeurosurgeryPrivolzhsky Research Medical UniversityNizhny Novgorod603005Russia

BACKGROUND Indirect decompression is one of the potential benefits of anterior reconstruction in patients with spinal *** the other hand,the reported rate of revision surgery after indirect decompression highlights the necessity of working out prediction models for the radiographic results of indirect decompression with assessing their clinical *** To assess factors that influence radiographic and clinical results of the indirect decompression in patients with stenosis of the lumbar *** This study is a single-center cross-sectional evaluation of 80 consecutive patients(17 males and 63 females)with lumbar spinal stenosis combined with the instability of the lumbar spinal *** underwent single level or bisegmental spinal instrumentation employing oblique lumbar interbody fusion(OLIF)with percutaneous pedicle screw *** results of the indirect decompression were assessed using computerized tomography,while MacNab scale was used to assess clinical *** After indirect decompression employing anterior reconstruction using OLIF,the statistically significant increase in the disc space height,vertebral canal square,right and left lateral canal depth were detected(Р<0.0001).The median(M)relative vertebral canal square increase came toМ=24.5%with 25%-75%quartile border(16.3%;33.3%)if indirect decompression was achieved by restoration of the segment *** patients with the reduction of the upper vertebrae slip,the median of the relative increase in vertebral canal square accounted for 49.5%with 25%-75%quartile border(2.35;99.75).Six out of 80 patients(7.5%)presented with unsatisfactory results because of residual nerve root *** critical values for lateral recess depth and vertebral canal square that were associated with indirect decompression failure were 3 mm and 80 mm2 *** Indirect decompression employing anterior reconstruction is achieved by the increase in disc height al

关键词： Indirect decompression Anterior reconstruction Central lumbar spinal stenosis Degenerative spondylolisthesis Lateral recess stenosis Spinal instability Oblique lateral interbody fusion

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Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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Neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： Carina Hromada Patrick Heimel Markus Kerbl LászlóGál Sylvia Nürnberger Barbara Schaedl James Ferguson Nicole Swiadek Xavier Monforte Johannes C.Heinzel Antal Nógrádi Andreas H.Teuschl-Woller David Hercher department Life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria Ludwig Boltzmann Institute for traumatology The Research Center in Cooperation with AUVAViennaAustria University Clinic of Dentistry Medical University of ViennaViennaAustria department of Plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria department of Hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

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Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

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Neural Regeneration Research 2025年第4期20卷 1135-1152页

作者： Yisheng Chen Zhongcheng Fan Zhiwen Luo Xueran Kang Renwen Wan Fangqi Li Weiwei Lin Zhihua Han Beijie Qi Jinrong Lin Yaying Sun Jiebin Huang Yuzhen Xu Shiyi Chen department of Sport Medicine Huashan HospitalFudan UniversityShanghaiChina department of Orthopedic Surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina department of Basic Medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina department of neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina department of orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina department of Infectious Diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural *** role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of *** used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other *** demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by *** underscores the intricate relationship between natural compounds such as nutlin-3 and immune *** comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma *** also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic ***-3a inhibited glioma cell proliferation and activated the p53 *** efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or *** using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway ***,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing *** results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma *** research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关键词： exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

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Acetabular components with or without screws in total hip arthroplasty

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World Journal of orthopedics 2017年第9期8卷 705-709页

作者： Murad Pepe Onur Kocadal Tamer Erener Kubilay Ceritoglu Ertugrul Aksahin Cem Nuri Aktekin department of orthopedics and traumatology Ankara Training and Research Hospital orthopedics and traumatology MedicalPark Hospital

AIM To compare the operation time, blood loss, and early outcomes of acetabular components with and without the *** Thirty patients who underwent cementless acetabular component with or without screw and whose follow-up exceeded one year period in total hip arthroplasty were evaluated. A posterior approach was used in all surgical procedures by one experienced surgeon. Demographic data, operation time, intra-and postoperative blood loss volume, follow-up clinical score, cup migration, and osteolysis were recorded. The Kolmogorov-Smirnov test was performed for testing the normality of study data. Mann-Whitney U test was used to analyze the intergroup differences. A P-value of ≤ 0.05 was considered statistically *** Acetabular components were used in 16(53.3%) patients with screw and 14(46.7%) without screw. After one year of follow-up, an osteolytic lesion of 3 mm was found in only one patient in the screw group. No cup migrationwas encountered. Intra-group mean Harris hip score significantly increased, but there was no significant intergroup difference. While the mean operation time of the screw group was 121.8 min(range; 95-140), it was 102.7 min(range; 80-120) in the no-screw group, and this difference was statistically significant(P = 0.002). The mean intraoperative/postoperative, and total blood loss were 556.6 mL(range: 350-800)/423.3 mL(range: 250-600), and 983.3 mL(range: 600-1350), respectively in the screw group; and 527 mL(range: 400-700)/456 mL(range: 230-600), and 983 mL(range: 630-1250), respectively in the no-screw group. The blood loss difference between the two groups was not significant. In the screw group, the operation time was 19.1 min longer than the no-screw group, and this difference was statistically *** Acetabular components with or without screw have similar results, but the use of screw increases the operation time significantly, while not changing the blood loss volume.

关键词： Hip arthroplasty Acetabular fixation With screw Without screw Operation time

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RESULTS OF DEBRIDEMENT TREATMENT FOR SPINAL PARALYSIS DUE TO TUBERCULOSIS IN CHILDREN

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中华医学杂志(英文版) 1965年第3期84卷 161-165+160页

作者：邸建德戴祥祺方先之 Pediatric Section Department of Orthopedics and Traumatology Tientsin People's Hospital Tientsin

The results of 49 cases of tuber-culosis of the spine complicated withspinal paralysis in children were *** cases were all treated by thedebridement method,and 96.8% of thecases treated by the anterolateral routehad complete recovery from *** paralysis in the majority ofchildren patients was *** was the first to become disturbedor *** was the next to beinvolved and to a less ***-ter function was usually normal or onlymildly *** on the cord was inmost cases due to necrotic disc tissue orsequestra which had been displaced intothe vertebral *** debride-ment operation the operator should ex-cise only the necessary portions of theribs and preserve the transverse pro-cesses,laminae and articular facets inorder to avoid postoperative scoliosisand lateral displacement of the spine.

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Spontaneous bilateral femur neck fracture secondary to grand mal seizure:A case report

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World Journal of Clinical Cases 2022年第30期10卷 11111-11115页

作者： Eyup Senocak department of orthopedics and traumatology Erzurum City HospitalErzurum 25144Turkey

BACKGROUND Spontaneous bilateral femur neck fracture is a rare entity in the general *** SUMMARY A 17-year-old immobile,developmentally delayed male with the sequelae of cerebral palsy fractured both femoral necks during a grand mal epileptic *** had been treated with valproic acid as an antiseizure medication for about 10years;otherwise,he had no history of drug *** laboratory analysis was normal except a marked vitamin D *** reduction and osteosynthesis with percutaneous cannulated screws were *** union was observed at 6 mo,and rapid postoperative rehabilitation was *** A femoral neck fracture may occur in a person with epilepsy presenting with hip pain in the emergency department.

关键词： Grand mal seizure Bilateral femur neck fracture Antiepileptic drugs Immobile patient Valproic acid use Spontan fracture Case report

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Treatment of knee osteochondritis dissecans with autologous tendon transplantation:Clinical and radiological results

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World Journal of orthopedics 2021年第11期12卷 867-876页

作者： Ahmet Ugur Turhan Sezgin Acil Orkun Gul Kerim Oner Ahmet Emin Okutan Muhammet Salih Ayas department of orthopedics and traumatology Karadeniz Technical University Faculty of MedicineTrabzon 61080Turkey department of orthopedics and traumatology Tirebolu State HospitalGiresun 28100Turkey department of orthopedics and traumatology Medical Park Trabzon HospitalTrabzon 61080Turkey department of orthopedics and traumatology Samsun Training and Research HospitalSamsun 55100Turkey department of orthopedics and traumatology Erzurum Regional Training and Research HospitalErzurum 25070Turkey

BACKGROUND Defect treatment with tendon autograft in osteochondral lesions has been published in the literature with an experimental study in *** demonstrate that it is possible to treat knee osteochondral lesions with the technique of autologous tendon *** To evaluate the clinical and radiological results of patients with knee osteochondral lesions who were treated with autologous tendon *** Twenty patients(22 knees)with osteochondritis dissecans(OCD)lesions involving the knee were treated with autologous tendon transplantation between *** lesions were International Cartilage Repair Society grade *** patients were evaluated clinically at final follow-up with knee injury and osteoarthritis outcome score(KOOS);and radiologically with magnetic resonance observation and cartilage repair tissue(MOCART)and Kellgren-Lawrence(KL)*** A total of 20 patients(22 knees)with a mean age of 25.5±6.8 years were *** average defect size was 4.2±2.1 cm^(2),and the average defect depth was 0.9±0.4 *** KOOS score was preoperatively 29.4±5.5 and was later found to be 81.5±5.9 after an average of 68.7±37.7 mo *** mean MOCART score was 56.2±***,all of the patients had KL grades of 0-1;during the follow-up period,80% of the patients showed no radiological progress of *** with less than 4 cm^(2) lesion had statistically significantly better overall KOOS than patients whose more than 4 cm^(2) lesion,particularly in sport and quality of life *** The autologous tendon transplantation is a single-step,safe,simple,cost-effective method for the treatment of knee OCD with satisfactory clinical and radiological outcomes,particularly in patients with less than 4 cm^(2) lesion.

关键词： Osteochondritis dissecans Knee Tendon Transplantation Autologous Peroneus

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