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Pharmacological interventions targeting the microcirculation following traumatic spinal cord injury

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Neural Regeneration Research 2024年第1期19卷 35-42页

作者： Rongrong Wang Jinzhu Bai Department of Spine and Spinal Cord Surgery Beijing Bo’ai HospitalChina Rehabilitation Research CenterBeijingChina school of rehabilitation medicine Capital Medical UniversityBeijingChina

Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve rse outcomes are closely related to the complex mechanism of spinal cord injury,the limited regenerative capacity of central neurons,and the inhibitory environment fo rmed by traumatic injury.Disruption to the microcirculation is an important pathophysiological mechanism of spinal cord injury.A number of therapeutic agents have been shown to improve the injury environment,mitigate secondary damage,and/or promote regeneration and repair.Among them,the spinal cord microcirculation has become an important target for the treatment of spinal cord injury.Drug inte rventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord injury.These drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neuro ns,axons,and glial cells.This review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury,including its structure and histopathological changes.Further,it summarizes the progress of drug therapies targeting the spinal cord mic rocirc ulation after spinal cord injury.

关键词： blood-spinal cord barrier drug therapy microcirculation microvascular blood flow neuroprotection pharmacological intervention pharmacotherapy spinal cord injury trauma

Development of a new cerebral ischemia reperfusion model of Mongolian gerbils and standardized evaluation system

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Animal Models and Experimental medicine 2024年第1期7卷 48-55页

作者： Ying Wu Caijiao Hu Zhihui Li Feiyang Li Jianyi Lv Meng Guo Xin Liu Changlong Li Xueyun Huo Zhenwen Chen Lifeng Yang Xiaoyan Du school of Basic medical Sciences Capital Medical UniversityBeijingChina Laboratory for Clinical medicine Capital Medical UniversityBeijingChina College of Veterinary medicine China Agricultural UniversityBeijingChina

Background:The Mongolian gerbil is an excellent laboratory animal for preparing the cerebral ischemia model due to its inherent deficiency in the circle of Willis.However,the low incidence and unpredictability of symptoms are caused by numerous complex variant types of the circle.Additionally,the lack of an evaluation system for the cer-ebral ischemia/reperfusion(I/R)model of gerbils has shackled the application of this model.Methods:We created a symptom-oriented principle and detailed neurobehavioral scoring criteria.At different time points of reperfusion,we analyzed the alteration in locomotion by rotarod test and grip force score,infarct volume by triphenyltetrazo-lium chloride(TTC)staining,neuron loss using Nissl staining,and histological charac-teristics using hematoxylin-eosin(H&E)straining.Results:With a successful model rate of 56%,32 of the 57 gerbils operated by our method harbored typical features of cerebral I/R injury,and the mortality rate in the male gerbils was significantly higher than that in the female gerbils.The suc-cessfully prepared I/R gerbils demonstrated a significant reduction in motility and grip strength at 1 day after reperfusion;formed obvious infarction;exhibited typi-cal pathological features,such as tissue edema,neuronal atrophy and death,and vacuolated structures;and were partially recovered with the extension of reperfu-sion time.Conclusion:This study developed a new method for the unilateral common carotid artery ligation I/R model of gerbil and established a standardized evaluation system for this model,which could provide a new cerebral I/R model of gerbils with more practical applications.

关键词： ischemia/reperfusion Mongolian gerbil standardized model system unilateral carotid occlusion

Upregulation of circ0000381 atienuates microglial/macrophage pyroptosis after spinal cord injury

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Neural Regeneration Research 2024年第6期19卷 1360-1366页

作者： Yan Zhang Wenkai Zhang Tao Liu Ziqian Ma Wenxiu Zhang Yun Guan Xueming Chen Central Laboratory Beijing Luhe Hospital Capital Medical University Department of Orthopedics Beijing Luhe Hospital Capital Medical University Department of Emergency medicine Aerospace Center Hospital Department of Anesthesiology and Critical Care medicine Johns Hopkins University School of Medicine Department of Neurological Surgery Johns Hopkins University School of Medicine

Neuroinflammation exacerbates secondary damage after spinal cord injury, while microglia/macrophage pyroptosis is important to neuroinflammation. Circular RNAs(circRNAs) play a role in the central nervous system. However, the functional role and mechanism of circRNAs in regulating microglia/macrophage pyroptosis after spinal cord injury are still poorly studied. In the present study, we detected microglia/macrophage pyroptosis in a female rat model of spinal cord injury, along with upregulated levels of circ0000381 in the spinal cord. Our further experimental results suggest that circ0000381 may function as a sponge to sequester endogenous microRNA423-3p(miR-423-3p), which can increase the expression of NOD-like receptor 3(NLRP3), a pyroptosis marker. Therefore, upregulation of circ0000381 may be a compensatory change after spinal cord injury to attenuate microglia/macrophage pyroptosis. Indeed, knockdown of circ0000381 expression exacerbated microglia/macrophage pyroptosis. Collectively, our findings provide novel evidence for the upregulation of circ0000381, which may serve as a neuroprotective mechanism to attenuate microglia/macrophage pyroptosis after spinal cord injury. Accordingly, circ0000381 may be a novel therapeutic target for the treatment of spinal cord injury.

关键词： circ0000381 inflammasome macrophage microglia miR-423-3p neuroinflammation neuroprotection NLRP3 pyroptosis RNA-Seq spinal cord injury

Conditioned medium from human dental pulp stem cells treats spinal cord injury by inhibiting microglial pyroptosis

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Neural Regeneration Research 2024年第5期19卷 1105-1111页

作者： Tao Liu Ziqian Ma Liang Liu Yilun Pei Qichao Wu Songjie Xu Yadong Liu Nan Ding Yun Guan Yan Zhang Xueming Chen Department of Orthopedic Surgery Beijing Luhe HospitalCapital Medical UniversityBeijingChina Department of Orthopedic Surgery Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina Department of Stomatology Beijing Luhe HospitalCapital Medical UniversityBeijingChina Department of Anesthesiology and Critical Care medicine School of MedicineJohns Hopkins UniversityBaltimoreMDUSA Department of Neurological Surgery School of MedicineJohns Hopkins UniversityBaltimoreMDUSA

Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear.In the present study,we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells.We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury,decreased expression of the microglial pyroptosis markers NLRP3,GSDMD,caspase-1,and interleukin-1β,promoted axonal and myelin regeneration,and inhibited the formation of glial scars.In addition,in a lipopolysaccharide-induced BV2 microglia model,conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,thereby promoting the recovery of neurological function after spinal cord injury.Therefore,conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.

关键词： BV2 conditioned medium dental pulp stem cells GSDMD microglia neuroinflammation NLRP3 pyroptosis spinal cord injury

Efficacy of Daoyin combined with lower limb robot as a comprehensive rehabilitation intervention for stroke patients: a randomized controlled trial

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Journal of Traditional Chinese medicine 2024年第3期44卷 530-536页

作者： TIAN Haolin YANG Yuanbin ZHANG Hu ZHAO Wenjing ZHOU Jing TIAN Jingfeng HE Long LI Xuechao SHEN Qinxuan SHUAI Mei Department of First rehabilitation Wangjing Hospital of China Academy of Chinese Medical Sciences Department of rehabilitation Shunyi HospitalBeijing Traditional Chinese Medicine Hospital school of Biological Science and medical Engineering Beihang University

OBJECTIVE: To assess the effectiveness of a comprehensive rehabilitation approach combining Traditional Chinese medicine Daoyin with lower limb robotics during the recovery phase of stroke patients.METHODS: Stroke patients meeting the specified criteria were randomly assigned to one of four groups using a random number table: Control group, Daoyin group, lower limb robot group(LLR group), and Daoyin and lower limb robot group(DLLR group). Each group received distinct treatments based on conventional rehabilitation training.The treatment duration spanned two weeks with two days of rest per week. Pre-and post-intervention assessments included various scales: Fugl-Meyer Assessment(FMA),Berg balance scale(BBS), Barthel index(BI), Fatigue Scale-14(FS-14), Pittsburgh sleep quality index(PSQI),Hamilton Anxiety Scale(HAMA), and Hamilton Depression Scale(HAMD).RESULTS: Statistically significant differences were observed in the lower limb function measured by FAM between the Control group(15 ± 5) and the DLLR group(18 ± 5)(P = 0.049). In the Barthel index, a statistically significant difference was noted between the Control group(54 ± 18) and the DLLR group(64 ± 11)(P = 0.041).Additionally, significant differences were found in the Berg balance scale between the Control group(21 ± 10)and the DLLR group(27 ± 8)(P = 0.024), as well as between the Control group(21 ± 10) and the LLR group(26 ± 10)(P = 0.048).CONCLUSION: The findings of this study suggest that the combined use of Daoyin and robotics not only enhances motor function in stroke patients but also has a positive impact on fatigue, sleep quality, and mood. This approach may offer a more effective rehabilitation strategy for stroke patients.

关键词： Daoyin lower limb robot randomized controlled trial rehabilitation stroke

Neuronal conversion from glia to replenish the lost neurons

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Neural Regeneration Research 2024年第7期19卷 1446-1453页

作者： Shiyu Liang Jing Zhou Xiaolin Yu Shuai Lu Ruitian Liu National Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijingChina school of Chemical Engineering University of Chinese Academy of SciencesBeijingChina Department of Geriatric rehabilitation Beijing Rehabilitation HospitalCapital Medical UniversityBeijingChina

Neuronal injury,aging,and cerebrovascular and neurodegenerative diseases such as cerebral infarction,Alzheimer’s disease,Parkinson’s disease,frontotemporal dementia,amyotrophic lateral sclerosis,and Huntington’s disease are characte rized by significant neuronal loss.Unfo rtunately,the neurons of most mammals including humans do not possess the ability to self-regenerate.Replenishment of lost neurons becomes an appealing therapeutic strategy to reve rse the disease phenotype.Transplantation of pluripotent neural stem cells can supplement the missing neurons in the brain,but it carries the risk of causing gene mutation,tumorigenesis,severe inflammation,and obstructive hydrocephalus induced by brain edema.Conversion of neural or non-neural lineage cells into functional neurons is a promising strategy for the diseases involving neuron loss,which may overcome the above-mentioned disadvantages of neural stem cell therapy.Thus far,many strategies to transfo rm astrocytes,fibroblasts,microglia,Muller glia,NG2 cells,and other glial cells to mature and functional neurons,or for the conversion between neuronal subtypes have been developed thro ugh the regulation of transcription factors,polypyrimidine tra ct binding protein 1(PTBP1),and small chemical molecules or are based on a combination of several factors and the location in the central nervous system.However,some recent papers did not obtain expected results,and discrepancies exist.Therefore,in this review,we discuss the history of neuronal transdifferentiation,summarize the strategies for neuronal replenishment and conversion from glia,especially astrocytes,and point out that biosafety,new strategies,and the accurate origin of the truly co nverted neurons in vivo should be focused upon in future studies.It also arises the attention of replenishing the lost neurons from glia by gene therapies such as up-regulation of some transc ription factors or downregulation of PTBP1 or drug interfe rence therapies.

关键词： astrocytes neural stem cells neurodegenerative diseases neuron polypyrimidine tract binding protein 1 repair reprogramming small molecule transcription factor transdifferentiation

Electroacupuncture at Sensitized Acupoints Relieves Somatic Referred Pain in Colitis Rats by Inhibiting Sympathetic-Sensory Coupling to Interferewith 5-HT Signaling Pathway

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Chinese Journal of Integrative medicine 2024年第2期30卷 152-162页

作者： YANG Ying QU Jin-yu GUO Hua ZHOU Hai-ying RUAN Xia PENG Ying-chun SHEN Xue-fang XIONG Jin WANG Yi-li school of Clinical medicine Chengdu Medical CollegeChengdu(610500)China Department of rehabilitation medicine the First Affliated Hospital of Chengdu Medical CollegeChengdu(610500)China Department of rehabilitation medicine West China HospitalSichuan University/West China School of NursingSichuan UniversityChengdu(610041)China Department of Neurology the First Affiliated Hospital of Chengdu Medical CollegeChengdu(610500)China

Objective:To investigate whether electroacupuncture(EA) at sensitized acupoints could reduce sympathetic-sensory coupling(SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine(5-HT)ergic neural pathways to relieve colitis and somatic referred pain,and explore the underlying mechanisms.Methods:Rats were treated with 5% dextran sodium sulfate(DSS) solution for 7 days to establish a colitis model.Twelve rats were randomly divided into the control and model groups according to a random number table(n=6).According to the Research on Rat Acupoint Atlas",sensitized acupoints and non-sensitized acupoints were determined.Rats were randomly divided into the control,model,Zusanli-EA(ST 36),Dachangshu-EA(BL 25),and Xinshu(BL 15) groups(n=6),as well as the control,model,EA,and EA+GR113808(a 5-HT inhibitor)groups(n=6).The rats in the control group received no treatment.Acupuncture was administered on 2 days after modeling using the stimulation pavameters:1 mA,2 Hz,for 30 min,with sparse and dense waves,for 14 consecutive days.GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days.Mechanical sensitivity was assessed with von Frey filaments.Body weight and disease activity index(DAI) scores of rats were determined.Hematoxylin and eosin staining was performed to observe colon histopathology.SSC was analyzed by immunofluorescence staining.Immunohistochemical staining was performed to detect 5-HT and substance P(SP) expressions.The calcitonin gene-related peptide(CGRP) in skin tissue and tyrosine hydroxylase(TH) protein levels in DRG were detected by Western blot.The levels of hyaluronic acid(HA),bradykinin(BK),prostaglandin I2(PGI2) in skin tissue,5-HT,tryptophan hydroxylase 1(TPH1),serotonin transporters(SERT),5-HT 3 receptor(5-HT3R),and 5-HT 4 receptor(5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay(ELISA).Results:BL 25 and ST 36 acupoints were determined as sensitized acupoints,and BL 15 acupoint was used as a non-sensitized acupoint

关键词： electroacupuncture sensitized acupoints sympathetic-sensory coupling 5-hydroxytryptamine neurogenic inflammation somaticreferredpain

Emergency physicians’ occupational risks in China

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World Journal of Emergency medicine 2024年第3期15卷 232-234页

作者： Huaying Jiang Jia Chang Rong Huang Xiayi Liang Manning Song Hejing Yuan Shuo Wang school of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 100105China Operation Room Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China school of Marxism Beijing University of Chinese MedicineBeijing 100105China Department of Infectious Diseases(Fever Clinic) Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing 100010China

With the rapid development of emergency medicine,emergency physicians are working around the clock,[1]including additional workloads due to sudden public health emergencies and disasters.Occupational risks for emergency physicians are significantly high due to an increasing number of patients with acute and severe diseases,an increased workload.

关键词： physician acute occupational

Short-term effects of cupping and scraping therapy for chronic nonspecific low-back pain:A prospective,multicenter randomized trial

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Journal of Integrative medicine 2024年第1期22卷 39-45页

作者： Jun-yan He Xiao-yu Tu Zi-fei Yin Hui Mu Ming-jun Luo Xing-yu Chen Wei-bin Cai Xue Zhao Can Peng Fan-fu Fang Can Lü Bai Li school of Traditional Chinese medicine Naval Medical UniversityShanghai 200433China Department of rehabilitation medicine and Physiotherapy the First Affiliated Hospital of Naval Medical UniversityShanghai 200433China Department of rehabilitation medicine and Training PLA 458 HospitalGuangzhou 510602Guangdong ProvinceChina No.3 Ward of Acupuncture rehabilitation Department Guangdong Second Traditional Chinese Medicine HospitalGuangzhou 510095Guangdong ProvinceChina

Background As one of the most common musculoskeletal ailments,chronic nonspecific low-back pain(CNLBP)causes persistent disability and substantial medical expenses.Epidemiological evidence shows that the incidence rate of CNLBP in young and middle-aged people who are demanded rapidly recovery and social contribution is rising.Recent guidelines indicate a reduced role for medicines in the management of CNLBP.Objective The present study investigates the short-term effects of cupping and scraping therapy using a medicated balm,compared to nonsteroidal anti-inflammatory drug(NSAID)with a capsaicin plaster,in the treatment of CNLBP.Design,setting,participants and interventions We designed a prospective multicenter randomized clinical trial enrolling patients from January 1,2022 to December 31,2022.A total of 156 patients with CNLBP were randomized into two parallel groups.Diclofenac sodium-sustained release tablets were administered orally to participants in the control group for one week while a capsaicin plaster was applied externally.Patients in the test group were treated with cupping and scraping using a medical device and medicated balm.Main outcome measures Primary outcome was pain recorded using the visual analogue scale(VAS).Two secondary outcomes were recorded using the Japanese Orthopedic Association low-back pain scale(JOA)and the traditional Chinese medicine(TCM)syndrome integral scale(TCMS)as assessment tools.Results Between baseline and postintervention,all changes in outcome metric scales were statistically significant(P<0.001).Compared to the control group,patients in the test group had a significantly greater treatment effect in all outcome variables,as indicated by lower VAS and TCMS scores and higher JOA scores,after the one-week intervention period(P<0.001).Further,according to the findings of multivariate linear regression analysis,the participants’pain(VAS score)was related to their marital status,age,smoking habits and body mass index.No adverse reactions were reported for any participants in t

关键词： Chronic nonspecific low-back pain Traditional Chinese medicine Cupping and scraping therapy