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Interorgan communication in neurogenic heterotopic ossification: the role of brain-derived extracellular vesicles

Bone Research 2024年第1期12卷 137-152页

作者： Weicheng Lu Jianfei Yan Chenyu Wang Wenpin Qin Xiaoxiao Han Zixuan Qin Yu Wei Haoqing Xu Jialu Gao Changhe Gao Tao Ye Franklin R.Tay Lina Niu Kai Jiao Department of Stomatology Tangdu Hospital&State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration&School of StomatologyThe Fourth Military Medical UniversityXi’anShaanxiChina State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration&National Clinical Research Center for Oral Diseases&Shaanxi Key Laboratory of Stomatology School of StomatologyThe Fourth Military Medical UniversityXi’anShaanxiChina The Dental College of Georgia Augusta UniversityAugustaGAUSA

Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury.Inflammasome-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal tissues.These proteins initiate inflammatory dysfunction,such as neurogenic heterotopic ossification.This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies.Accordingly,a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two issues.Histological examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast pyroptosis.The relationships among brain-derived extracellular vesicles,fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo.Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo.The present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury.

关键词： neurogenic ossification pathogenesis

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Timing umbilical therapy in treatment of neurogenic bladder after spinal cord injury based on midnight-noon and ebb-flow doctrine:a randomized controlled trial

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China Medical Abstracts(Internal Medicine) 2024年第1期41卷 7-7页

作者：王东利 Dept Orthopedics Traumatol&RehabCangzhou Integr Chin&West Med HospCangzhou 061000

Objective To observe the clinical efficacy of timing umbilical therapy for neurogenic bladder after spinal cord injury based on the midnight-noon and ebb-flow doctrine.Methods Sixty patients with neurogenic bladder af... 详细信息

关键词： bladder neurogenic clinical

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A biomimetic piezoelectric scaffold with sustained Mg^(2+)release promotes neurogenic and angiogenic differentiation for enhanced bone regeneration

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Bioactive Materials 2023年第7期25卷 399-414页

作者： Liangyu Wang Yanyun Pang Yujing Tang Xinyu Wang Daixing Zhang Xu Zhang Yingjie Yu Xiaoping Yang Qing Cai State Key Laboratory of Organic-Inorganic Composites Beijing Laboratory of Biomedical MaterialsBeijing University of Chemical TechnologyBeijing100029China School and Hospital of Stomatology Tianjin Medical UniversityTianjin300070China SINOPEC(Beijing)Research Institute of Chemical Industry Co. Ltd.Beijing100013China Foshan(Southern China)Institute for New Materials Foshan528200GuangdongChina

Natural bone is a composite tissue made of organic and inorganic components,showing piezoelectricity.Whitlockite(WH),which is a natural magnesium-containing calcium phosphate,has attracted great attention in bone formation recently due to its unique piezoelectric property after sintering treatment and sustained release of magnesium ion(Mg^(2+)).Herein,a composite scaffold(denoted as PWH scaffold)composed of piezoelectric WH(PWH)and poly(ε-caprolactone)(PCL)was 3D printed to meet the physiological demands for the regeneration of neuro-vascularized bone tissue,namely,providing endogenous electric field at the defect site.The sustained release of Mg^(2+)from the PWH scaffold,displaying multiple biological activities,and thus exhibits a strong synergistic effect with the piezoelectricity on inhibiting osteoclast activation,promoting the neurogenic,angiogenic,and osteogenic differentiation of bone marrow mesenchymal stromal cells(BMSCs)in vitro.In a rat calvarial defect model,this PWH scaffold is remarkably conducive to efficient neo-bone formation with rich neurogenic and angiogenic expressions.Overall,this study presents the first example of biomimetic piezoelectric scaffold with sustained Mg^(2+)release for promoting the regeneration of neuro-vascularized bone tissue in vivo,which offers new insights for regenerative medicine.

关键词： Bone regeneration Piezoelectricity neurogenic Angiogenic Osteogenic

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neurogenic nitric oxide facilitates the central nociceptive transmission of migraine attacks

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Neural Regeneration Research 2011年第3期6卷 213-218页

作者： Wang, Hebo Qi, Huijun Yu, Shengyuan Yang, Sumian Liu, Ruozhuo Hebei Gen Hosp Dept Neurol Shijiazhuang 050051 Hebei Peoples R China Hebei Gen Hosp Dept Emergency Shijiazhuang 050051 Hebei Peoples R China Chinese Peoples Liberat Army Gen Hosp Dept Neurol Beijing 100853 Peoples R China

Recent studies have shown that nitric oxide （NO） can induce migraine attacks at three possible sites of action： nitroxidergic nerves, the vascular endothelium, and the central nervous system. Most previous studies have focused on the former two sites of action. Several experiments using exogenic NO donors have suggested that nitroglycerin may induce migraine via central mechanisms. However, few studies have investigated the source of the NO involved in the central mechanisms of migraine. The present study used a cat model of migraine to represent migraine attacks in humans. We performed immunochemical staining of successive frozen sections of the brainstem and upper cervical spinal cord, and then used c-Fos protein expression to label nerve cell activation. We observed the effects of N^ω-nitro-L-arginine methyl ester （L-NAME）, a non-selective nitric oxide synthase （NOS） inhibitor, and 7-nitroindozole （7-NI）, a selective neuronal NOS inhibitor, on c-Fos and nNOS expression, which were induced by electrical stimulation to the dura mater near the superior sagittal sinus. The results demonstrated that c-Fos or nNOS immunoreactive cells was concentrated in the superficial layers （laminae Ⅰ and Ⅱ） of the spinal nucleus of trigeminal nerve. L-NAME and 7-NI pre-treatment significantly decreased c-Fos and neurogenic NOS expression; and there was a significant linear correlation between c-Fos and NOS expression （r = 0.858 2, P 〈 0.01）. These findings suggest that neurogenic NO could facilitate migraine nociceptive transmission to second-order neurons of the trigeminal nerve. However, L-NAME and 7-NI may block the activation of neurons in the spinal nucleus of the trigeminal nerve by inhibiting NO synthesis, and thereby attenuate acute migraine attacks.

关键词： migraine c-Fos nitric oxide dura mater neurogenic superior sagittal sinus

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MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1

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International Journal of Oral Science 2023年第4期15卷 649-663页

作者： Chen Zhang Weilong Ye Mengyao Zhao Lujue Long Dengsheng Xia Zhipeng Fan Laboratory of Molecular Signaling and Stem Cells Therapy Beijing Key Laboratory of Tooth Regeneration and Function ReconstructionBeijing Stomatological HospitalSchool of StomatologyCapital Medical UniversityBeijingChina Department of Dental Emergency Beijing Stomatological HospitalSchool of StomatologyCapital Medical UniversityBeijingChina Beijing Laboratory of Oral Health Capital Medical UniversityBeijingChina Research Unit of Tooth Development and Regeneration Chinese Academy of Medical SciencesBeijingChina

Mesenchymal stem cell(MSC)-based therapy has emerged as a promising treatment for spinal cord injury(SCI),but improving the neurogenic potential of MSCs remains a challenge.Mixed lineage leukemia 1(MLL1),an H3K4me3 methyltransferases,plays a critical role in regulating lineage-specific gene expression and influences neurogenesis.In this study,we investigated the role and mechanism of MLL1 in the neurogenesis of stem cells from apical papilla(SCAPs).We examined the expression of neural markers,and the nerve repair and regeneration ability of SCAPs using dynamic changes in neuron-like cells,immunofluorescence staining,and a SCI model.We employed a coimmunoprecipitation(Co-IP)assay,real-time RT-PCR,microarray analysis,and chromatin immunoprecipitation(ChIP)assay to investigate the molecular mechanism.The results showed that MLL1 knock-down increased the expression of neural markers,including neurogenic differentiation factor(NeuroD),neural cell adhesion molecule(NCAM),tyrosine hydroxylase(TH),βIII-tubulin and Nestin,and promoted neuron-like cell formation in SCAPs.In vivo,a transplantation experiment showed that depletion of MLL 1 in SCAPs can restore motor function in a rat SCI model.MLL1 can combine with WD repeat domain 5(WDR5)and WDR5 inhibit the expression of neural markers in SCAPs.MLL1 regulates Hairy and enhancer of split 1(HES1)expression by directly binds to HES1 promoters via regulating H3K4me3 methylation by interacting with WDR5.Additionally,HES1 enhances the expression of neural markers in SCAPs.Our findings demonstrate that MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1.These results provide a potential therapeutic target for promoting the recovery of motor function in SCI patients.

关键词： HES1 neurogenic MLL1

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Acute flaccid paralysis and neurogenic respiratory failure associated with enterovirus D68 infection in children: Report of two cases

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World Journal of Clinical Cases 2021年第14期9卷 3327-3333页

作者： Yv Zhang Sheng-Yuan Wang Da-Zhi Guo Shu-Yi Pan Yan Lv Department of Hyperbaric Oxygen The Sixth Medical Center of PLA General HospitalBeijing 100048China

BACKGROUND Acute flaccid paralysis(AFP)and neurogenic respiratory failure rarely occur in children.At the end of 2018,some children with such symptoms were admitted to our hospital.In this study,we aimed to assess two children with AFP and neurogenic respiratory failure associated with enterovirus D68(EV-D68).CASE SUMMARY Two children admitted to our hospital presented with symptoms and imaging results different from those of acute disseminated encephalomyelitis and hand,foot,and mouth disease.Their main symptoms were AFP and neurogenic respiratory failure.Magnetic resonance imaging showed severe inflammatory injury mainly to the anterior horn cells of the spinal cord.Blood and cerebrospinal fluid samples were collected to assess for pathogens,including bacteria,tuberculosis,cryptococcus,herpes virus,and coxsackie virus,and the results were negative.At the beginning,the two cases were not assessed for EV-D68 in the nasopharyngeal,blood,and cerebrospinal fluid specimens.About 2 mo later,EVD68 was detected in the stool sample of one of the cases.The symptom of AFP was caused by injury to the anterior horn cells at levels C5-L5 of the spinal cord,while neurogenic respiratory failure was at levels C3-C5.CONCLUSION We should pay attention to the detection and diagnosis of EV-D68 and make efforts to develop antivirus drugs and vaccines.

关键词： Infection Enterovirus D68 Flaccid Paralysis neurogenic Respiratory failure Case report

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TAZ and myostatin involved in muscle atrophy of congenital neurogenic clubfoot

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World Journal of Clinical Cases 2019年第16期7卷 2238-2246页

作者： Jia-Xing Sun Ze-Yu Yang Li-Mei Xie Bing Wang Ning Bai Ai-Lu Cai Department of Ultrasound Shengjing Hospital of China Medical UniversityShenyang 110004Liaoning ProvinceChina Key Laboratory of Medical Cell Biology Ministry of EducationInstitute of Translational MedicineChina Medical UniversityLiaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and PreventionShenyang 110004Liaoning ProvinceChina

BACKGROUND Muscular atrophy is the basic defect of neurogenic clubfoot.Muscle atrophy of clubfoot needs more scientific and reasonable imaging measurement parameters to evaluate.The Hippo pathway and myostatin pathway may be directly correlated in myogenesis.In this study,we will use congenital neurogenic clubfoot muscle atrophy model to verify in vivo.Further,the antagonistic mechanism of TAZ on myostatin was studied in the C2C12 cell differentiation model.AIM To identify muscle atrophy in fetal neurogenic clubfoot by ultrasound imaging and detect the expression of TAZ and myostatin in gastrocnemius muscle.To elucidate the possible mechanisms by which TAZ antagonizes myostatin-induced atrophy in an in vitro cell model.METHODS Muscle atrophy in eight cases of fetal unilateral clubfoot with nervous system abnormalities was identified by 2D and 3D ultrasound.Western blotting and immunostaining were performed to detect expression of myostatin and TAZ.TAZ overexpression in C2C12 myotubes and the expression of associated proteins were analyzed by western blotting.RESULTS The maximum cross-sectional area of the fetal clubfoot on the varus side was reduced compared to the contralateral side.Myostatin was elevated in the atrophied gastrocnemius muscle,while TAZ expression was decreased.They were negatively correlated.TAZ overexpression reversed the diameter reduction of the myotube,downregulated phosphorylated Akt,and increased the expression of forkhead box O4 induced by myostatin.CONCLUSION Ultrasound can detect muscle atrophy of fetal clubfoot.TAZ and myostatin are involved in the pathological process of neurogenic clubfoot muscle atrophy.TAZ antagonizes myostatin-induced myotube atrophy,potentially through regulation of the Akt/forkhead box O4 signaling pathway.

关键词： Congenital clubfoot neurogenic Muscle atrophy Myostatin TAZ

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Robotic Transthoracic First Rib Resection for neurogenic Thoracic Outlet Syndrome

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World Journal of Cardiovascular Surgery 2022年第1期12卷 1-11页

作者： Farid Gharagozloo Mark Meyer Center for Advanced Thoracic Surgery Advent Health Celebration University of Central Florida Celebration USA

Purpose: neurogenic Thoracic Outlet Syndrome accounts for over 95% of patients with TOS. We report a single institution experience with robotic first rib resection in patients with neurogenic TOS. Methods: The diagnosis of NTOS was made in patients in whom all specific localizing and diagnostic orthopedic and neurologic conditions were ruled out. Preoperative diagnostic tests included a comprehensive history and physical exam, Chest X-ray, Chest CT, MRI if the cervical spine, Nerve conduction studies, and Magnetic Resonance angiography of the Thoracic outlet with arm maneuvers (MRA). Patients with NTOS who underwent robotic first rib resection with disarticulation of the costosternal joint and scalenectomy. Results: There were 137 patients (47 men and 90 women). Mean age was 34 ± 9.5 years. Operative time was 93 minutes ± 10.3 minutes. There were no intraoperative complications. There was no injury to the subclavian vessels during the dissection. There were no neurovascular complications. There was no 30 or 90 day mortality. Quick DASH Scores (Mean ± SEM) decreased from 60.3+/2.1 preoperatively to 5 ± 2.3 in the immediate postoperative period, and 3.5+/1.1 at 6 months. (P neurogenic Thoracic Outlet Syndrome.

关键词： Thoracic Outlet Syndrome neurogenic Robotic Surgery Minimally Invasive Surgery

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Midline synovial and ganglion cysts causing neurogenic claudication

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World Journal of Clinical Cases 2013年第9期1卷 285-289页

作者： Jonathan Pindrik Mohamed Macki Mohamad Bydon Zahra Maleki Ali Bydon Department of Neurosurgery Johns Hopkins University School of Medicine Department of Pathology Johns Hopkins University School of Medicine

Typically situated posterolateral in the spinal canal, intraspinal facet cysts often cause radicular symptoms. Rarely, the midline location of these synovial or ganglion cysts may cause thecal sac compression leading to neurogenic claudication or cauda equina syndrome. This article summarizes the clinical presentation, radiographic appearance, and management of three intraspinal, midline facet cysts. Three patients with symptomatic midline intraspinal facet cysts were retrospectively reviewed. Documented clinical visits, operative notes, histopathology reports, and imaging findings were investigated for each patient. One patient presented with neurogenic claudication while two patients developed partial, subacute cauda equina syndrome. All 3 patients initially responded favorably to lumbar decompression and midline cyst resection; however, one patient required surgical stabilization 8 mo later. Following the three case presentations, we performed a thorough literature search in order to identify articles describing intraspinal cystic lesions in lateral or midline locations. Midline intraspinal facet cysts represent an uncommon cause of lumbar stenosis and thecal sac compression. Such entities should enter the differential diagnosis of midline posterior cystic lesions. Midline cysts causing thecal sac compression respond favorably to lumbar surgical decompression and cyst resection. Though laminectomy is a commonly performed operation, stabilization may be required in cases of spondylolisthesis or instability.

关键词： Midline Synovial Ganglion Intraspinal Cyst neurogenic Claudication Laminectomy Facet

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Impact of Adjuvant Radiotherapy and Reversibility of neurogenic Bladder on Bladder Storage Function and Impact of Urethral Resistance on Bladder Emptying Function after Radical Hysterectomy

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Open Journal of Urology 2017年第12期7卷 252-265页

作者： Noritoshi Sekido Takayuki Yoshino Eiichiro Takaoka Natsui Waku Ken Tanaka Hiroyuki Nishiyama Hiroyuki Ochi Toyomi Satoh Department of Urology Tsukuba University Hospital Ibaraki Japan Department of Urology School of Medicine Faculty of Medicine Toho University Ohashi Medical Center Tokyo Japan Urology and Andrology Majors of Medical Sciences Graduate School of Comprehensive Human Sciences University of Tsukuba Ibaraki Japan Departments of Obstetrics and Gynecology Faculty of Medicine University of Tsukuba Ibaraki Japan

Purpose: To clarify which patients need careful neurourological management after abdominal radical hysterectomy (RH) by investigating the effects of adjuvant radiotherapy and reversibility of neurogenic bladder (NB) on the storage function as well as the effects of urethral resistance on the emptying function. Methods: Data from sixty-two patients referred to our NB clinic after RH were retrospectively reviewed. Findings of urodynamic studies performed at 3 (UDS-1) and 12 (UDS-2) months after treatment were compared, and logistic analysis was used to calculate the odds ratio (OR) of the effects of radiotherapy and irreversible NB on decreased bladder capacity and decreased compliance. Irreversible NB was defined as the need for clean intermittent catheterization at the last follow-up. Results: At the median follow-up period of 41 months, 60% of the patients continued to require clean intermittent catheterization. Of patients with irreversible NB and radiotherapy, 80% had decreased bladder capacity and decreased compliance at UDS-2. For decreased bladder capacity and decreased compliance, ORs of adjuvant radiotherapy at UDS-2 were 38.42 (p Conclusions: Careful neurourological follow-up after RH is mandatory for patients who undergo adjuvant radiotherapy and have irreversible NB with impaired urethral relaxation.

关键词： Urinary Bladder neurogenic Clean Intermittent Catheterization Hysterectomy Radiotherapy

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