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Saikosaponin a increases interleukin-10 expression and inhibits scar formation after sciatic nerve injury

Neural Regeneration Research 2018年第9期13卷 1650-1656页

作者： Meng-Qiang Huang Xiao-Yu Cao Xu-Yi Chen Ying-Fu Liu Shuang-Long Zhu Zhong-Lei Sun Xian-Bin Kong Jing-Rui Huo Sai Zhang Yun-Qiang Xu Graduate School Tianjin Medical University Department of Orthopedics Tianjin Medical University General Hospital Department of Rehabilitation Medicine First Affiliated Hospital of Anhui Medical University Tianjin Key Laboratory of neurotrauma Repair Institute of Traumatic Brain Injury and NeuroscienceCenter for Neurology and Neurosurgery of Affiliated HospitalLogistics University of Chinese People's Armed Police Force Science and Technology Experiment Center Cangzhou Medical College Graduate School Jinzhou Medical University Graduate School Tianjin University of Traditional Chinese Medicine

Nerve scarring after peripheral nerve injury can severely hamper nerve regeneration and functional ***,the anti-inflammatory cytokine,interleukin-10,can inhibit nerve scar *** a（SSa） is a monomer molecule extracted from the Chinese medicine,*** can exert anti-inflammatory effects in spinal cord injury and traumatic brain ***,it has not been shown whether SSa can play a role in peripheral nerve *** this study,rats were randomly assigned to three *** the sham group,the left sciatic nerve was directly sutured after *** the sciatic nerve injury（SNI）＋ SSa and SNI groups,the left sciatic nerve was sutured and continuously injected daily with SSa（10 mg/kg） or an equivalent volume of saline for 7 *** linked immunosorbent assay results demonstrated that at 7 days after injury,interleukin-10 level was considerably higher in the SNI ＋ SSa group than in the SNI *** staining and western blot assay demonstrated that at 8 weeks after injury,type I and III collagen content was lower and nerve scar formation was visibly less in the SNI ＋ SSa group compared with the SNI ***,sciatic functional index and nerve conduction velocity were improved in the SNI ＋ SSa group compared with the SNI *** results confirm that SSa can increase the expression of the anti-inflammatory factor,interleukin-10,and reduce nerve scar formation to promote functional recovery of injured sciatic nerve.

关键词： nerve regeneration saikosaponin a anti-inflammatory factor inflammation interleukin-l O nerve scar peripheral nerve injury sciatic nerve injury sciatic functional index nerve conduction velocity neuroelectrophysiological function neural regeneration

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Three-dimensional bioprinting collagen/silk fibroin scaffold combined with neural stem cells promotes nerve regeneration after spinal cord injury

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Neural Regeneration Research 2020年第5期15卷 959-968页

作者： Ji-Peng Jiang Xiao-Yin Liu Fei Zhao Xiang Zhu Xiao-Yin Li Xue-Gang Niu Zi-Tong Yao Chen Dai Hui-You Xu Ke Ma Xu-Yi Chen Sai Zhang Department of Thoracic Surgery General Hospital of People’s Liberation Army (PLA)BeijingChina Tianjin Key Laboratory of neurotrauma Repair Institute of Traumatic Brain Injury and NeuroscienceCenter for Neurology and Neurosurgery of Chinese People’s Armed Police Force (PAP) Medical CenterTianjinChina Tianjin Medical University TianjinChina Department of Neurology Luoyang First Hospital of Traditional Chinese MedicineLuoyangHenan ProvinceChina Department of Neurosurgery Fourth Central Hospital of TianjinTianjinChina

Many studies have shown that bio-scaffolds have important value for promoting axonal regeneration of injured spinal ***,cell transplantation and bio-scaffold implantation are considered to be effective methods for neural *** study was designed to fabricate a type of three-dimensional collagen/silk fibroin scaffold (3D-CF) with cavities that simulate the anatomy of normal spinal *** scaffold allows cell growth in vitro and in *** observe the effects of combined transplantation of neural stem cells (NSCs) and 3D-CF on the repair of spinal cord *** Sprague-Dawley rats were divided into four groups: sham (only laminectomy was performed),spinal cord injury (transection injury of T10 spinal cord without any transplantation),3D-CF (3D scaffold was transplanted into the local injured cavity),and 3D-CF + NSCs (3D scaffold co-cultured with NSCs was transplanted into the local injured ***,imaging,hematoxylin-eosin staining,argentaffin staining,immunofluorescence staining,and western blot assay were *** from the sham group,neurological scores were significantly higher in the 3D-CF + NSCs group compared with other ***,latency of the 3D-CF + NSCs group was significantly reduced,while the amplitude was significantly increased in motor evoked potential *** results of magnetic resonance imaging and diffusion tensor imaging showed that both spinal cord continuity and the filling of injury cavity were the best in the 3D-CF + NSCs ***,regenerative axons were abundant and glial scarring was reduced in the 3D-CF + NSCs group compared with other *** results confirm that implantation of 3D-CF combined with NSCs can promote the repair of injured spinal *** study was approved by the Institutional Animal Care and Use Committee of People’s Armed Police Force Medical Center in 2017 (approval No.2017-0007.2).

关键词： 3D bioprinting collagen diffusion tensor imaging functional recovery magnetic resonance imaging nerve regeneration neural regeneration neural stem cell scaffold silk fibroin spinal cord injury

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Exendin-4 inhibits high-altitude cerebral edema by protecting against neurobiological dysfunction

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Neural Regeneration Research 2018年第4期13卷 653-663页

作者： Zhong-Lei Sun Xian-Feng Jiang Yuan-Chi Cheng Ying-Fu Liu Kai Yang Shuang-Long Zhu Xian-Bin Kong Yue Tu Ke-Feng Bian Zhen-Lin Liu Xu-Yi Chen Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces Institute of Traumatic Brain Trauma and Neurological of CAPF Neurotrauma Repair Key Laboratory of Tianjin Tianjin China Jinzhou Medical University Jinzhou Liaoning Province China Tianjin Medical University Tianjin China Central Hospital of Fengxian District of Shanghai Shanghai China Logistics University of People's Armed Police Force Tianjin China The No. 2 Hospital of Nanjing Nanjing Jiangsu Province China Tianjin University of Traditional Chinese Medicine Tianjin China

The anti-inflammatory and antioxidant effects of exendin-4（Ex-4） have been reported ***,whether（Ex-4） has anti-inflammatory and antioxidant effects on high-altitude cerebral edema（HACE） remains poorly *** this study,two rat models of HACE were established by placing rats in a hypoxic environment with a simulated altitude of either 6000-or 7000-m above sea level（MASL） for 72 *** altitude of 7000 MASL with 72-hours of hypoxia was found to be the optimized experimental paradigm for establishing HACE ***,in rats where a model of HACE was established by introducing them to a 7000 MASL environment with 72-hours of hypoxia treatment,2,10 and,100 μg of Ex-4 was intraperitoneally *** open field test and tail suspension test were used to test animal *** methods were used to detect change in inflammatory ***-eosin staining was performed to determine pathological changes to brain ***/dry weight ratios were used to measure brain water *** blue leakage was used to determine blood-brain barrier ***-linked immunosorbent assay（ELISA） was performed to measure markers of inflammation and oxidative stress including superoxide dismutase,glutathione,and malonaldehyde values,as well as interleukin-6,tumor necrosis factor-alpha,cyclic adenosine monophosphate levels in the brain *** blot analysis was performed to determine the levels of occludin,ZO-1,SOCS-3,vascular endothelial growth factor,EPAC1,nuclear factor-kappa B,and *** results demonstrate that Ex-4 preconditioning decreased brain water content,inhibited inflammation and oxidative stress,alleviated brain tissue injury,maintain blood-brain barrier integrity,and effectively improved motor function in rat models of *** findings suggest that Ex-4 exhibits therapeutic potential in the treatment of HACE.

关键词： high-altitude cerebral edema exendin-4 cyclic adenosine monophosphate EPACI suppressor of cytokine signaling 3 vascular endothelial growth factor hypoxia inflammation oxidative stress

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Protective Effects of Calpain Inhibition on Neurovascular unit Injury through Downregulating Nuclear Factor-KB- related Inflammation during Traumatic Brain Injury in Mice

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Chinese Medical Journal 2017年第2期130卷 187-198页

作者： Xiao-Gang Tao Jing-Hua Shi Shu-Yu Hao Xue-Tao Chen Bai-Yun Liu Department of Neurosurgery Beijing Tian Tan Hospital Capital Medical University Beijing 100050 China Department of Otolaryngology Beijing Tian Tan Hospital Capital Medical University Beijing 100050 China Department of neurotrauma Beijing Neurosurgical Institute Capital Medical University Beijing 100050 China

Background： In addition to neurons, all components of the neurovascular unit （NVU）, such as glial, endothelial, and basal membranes, are destroyed during traumatic brain injury （TBI）. Previous studies have shown that excessive stimulation ofcalpain is crucial for cerebral injury after traumatic insult. The objective of this study was to investigate whether calpain activation participated in NVU disruption and edema formation in a mouse model of controlled cortical impact （CCI）. Methods： One hundred and eight mice were divided into three groups： the sham group, the control group, and the MDL28170 group. MDL28170 （20 mg/kg）, an efficient calpain inhibitor, was administered intraperitoneally at 5 rain, 3 h, and 6 h after experimental CCI. We then measured neurobehavioral deficits, calpain activity, inflammatory mediator levels, blood-brain barrier （BBB） disruption, and NVU deficits using electron microscopy and histopathological analysis at 6 h and 24 h after CCI. Results： The MDL28170 treatment significantly reduced the extent of both cerebral contusion （MDL28170 vs. vehicle group, 16.90 ± 1.01 mm3 and 17.20±1.17 mm3 vs. 9.30 ± 1.05 mm^3 and 9.90 ± 1.17 mm3, both P 〈 0.001 ） and edema （M DL28170 vs. vehicle group, 80.76 ± 1.25% and 82.00 ± 1.84% vs. 82.55 ± 1.32% and 83.64 ± 1.25%, both P 〈 0.05）, improved neurological scores （MDL28170 vs. vehicle group, 7.50 ±0.45 and 6.33 ±0.38 vs. 12.33 ± 0.48 and 11.67±0.48, both P 〈 0.001）, and attenuated NVU damage resulting （including tight junction （TJ）, basement membrane, BBB, and neuron） from CCI at 6 h and 24 h. Moreover, MDL28170 markedly downregulated nuclear factor-κB-related inflammation （tumor necrosis factor-α [TNF-α]： MDL28170 vs. vehicle group, 1.15 ± 0.07 and 1.62± 0.08 vs. 1.59±0.10 and 2.18± 0.10, both P 〈 0.001 ： inducible nitric oxide synthase： M DL28170 vs. vehicle group, 4.51± 0.23 vs. 6.23± 0.12, P 〈 0.001 at 24 h; intracellular adhesion molecule- I ： MDL28170 vs. vehicle group, 1.45± 0.13 vs. 1.70 ± 0.12, P

关键词： Calpain Inflammation: Neurovascular unit: Nuclear Factor-κB Traumatic Brain Injury

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Engineered neuronal microtissue provides exogenous axons for delayed nerve fusion and rapid neuromuscular recovery in rats

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Bioactive Materials 2022年第12期7卷 339-353页

作者： Justin C.Burrell Suradip Das Franco A.Laimo Kritika S.Katiyar Kevin D.Browne Robert B.Shultz Vishal J.Tien Phuong T.Vu Dmitriy Petrov Zarina SAli Joseph M.Rosen D.Kacy Cullen Center for Brain Injury&Repair Department of NeurosurgeryPerelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPAUSA Department of Bioengineering School of Engineering&Applied ScienceUniversity of PennsylvaniaPhiladelphiaPAUSA Center for neurotrauma Neurodegeneration&RestorationCorporal Michael J.Crescenz Veterans Affairs Medical CenterPhiladelphiaPA19104USA Axonova Medical LLCPhiladelphiaPAUSA Dartmouth-Hitchcock Medical Center Division of Plastic SurgeryDartmouth CollegeLebanonNHUSA

Nerve injury requiring surgical repair often results in poor functional recovery due to the inability of host axons to re-grow long distances and reform meaningful connections with the target muscle. While surgeons can re-route local axon fascicles to the target muscle, there are no technologies to provide an exogenous source of axons without sacrificing healthy nerves. Accordingly, we have developed tissue engineered neuromuscular interfaces (TE-NMIs) as the first injectable microtissue containing motor and sensory neurons in an anatomically-inspired architecture. TE-NMIs provide axon tracts that are intended to integrate with denervated distal structures and preserve regenerative capacity during prolonged periods without host innervation. Following implant, we found that TE-NMI axons promoted Schwann cell maintenance, integrated with distal muscle, and preserved an evoked muscle response out to 20-weeks post nerve transection in absence of innervation from host axons. By repopulating the distal sheath with exogenous axons, TE-NMIs also enabled putative delayed fusion with proximal host axons, a phenomenon previously not achievable in delayed repair scenarios due to distal axon degeneration. Here, we found immediate electrophysiological recovery after fusion with proximal host axons and improved axon maturation and muscle reinnervation at 24-weeks post-transection (4-weeks following delayed nerve fusion). These findings show that TE-NMIs provide the potential to improve functional recovery following delayed nerve repair.

关键词： Nerve regeneration Neuromuscular injury Muscle preservation Tissue engineering Microtissue Axon fusion

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TGFβ signaling-induced miRNA participates in autophagic regulation by targeting PRAS40 in mesenchymal subtype of glioblastoma

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Cancer Biology & Medicine 2020年第3期17卷 664-675页

作者： Yingbin Xie Luyue Chen Junhu Zhou Qixue Wang Chao Yang Can Xu Xiangyu Fan Yanli Tan Yanan Wang Chunsheng Kang Chuan Fang Department of Neurosurgery Hebei University Affiliated HospitalBaoding 071000China Laboratory of Neuro-0neology Tianjin Neurological InstituteDepartment of NeurosurgeryTianjin Medical University General Hospital and Key Laboratory of NeurotraumaVariationand RegenerationMinistry of Education and Tianjin Municipal GovernmentTianjin 300052China Department of Neurosurgery Zhongshan Hospital Xiamen UniversityXiamen 361004China Department of Pathology Hebei University Affiliated HospitalBaoding 071000China Affiliated Cancer Hospital and Institute of Guangzhou Medical University Guangzhou 510095China

Objective:Mesenchymal subtype of glioblastoma(mesGBM)is a refractory disease condition characterized by therapeutic failure and tumor *** transforming growth factor-β(TGF-β)signaling could be a signature event in mesGBM,which leads to dysregulation of downstream targets and contribute to malignant *** this study we aimed to investigate the hyperactive TGFβsignaling-mediated pathogenesis and possible downstream targets for the development of novel therapeutic interventions for ***:GBM-BioDP is an online resource for accessing and displaying interactive views of the TCGA GBM data *** sequencing followed by bioinformatic analysis was performed to identify dysregulated *** prediction by MR-microT and dual luciferase reporter assay were utilized to confirm the predicted target of novel_***-8 assays was used to assesse cell *** miRNA manipulation was proceeded by cell transfection and lentivirus delivery.A plasmid expressing GFP-LC3 was introduced to visualize the formation of *** GBM model was constructed forin vivo ***:TGFβ1 and TGFβreceptor type II(TβRII)were exclusively upregulated in mesGBM(P<0.01).Dysregulated miRNAs were identified after LY2109761(a TβRI/II inhibitor)treatment in a mesGBM-derived cell line,and novel_miR56 was selected as a promising candidate for further functional ***_miR56 was found to potentially bind to PRAS40 via seed region complementarity in the 3'untranslated region,and we also confirmed that PRAS40 is a direct target of novel_miR56 in glioma *** vitro,over expression of novel_miR56 in tumor cells significantly promoted proliferation and inhibited autophagy(P<0.05).The expression levels of P62/SQSTM was significantly increased accompanied by the decrease of BECN1 and LC3B-II/I,which indicated that autophagic activity was reduced after novel_miR56 *** addition,over expression of novel_miR56 also

关键词： Autophagy glioblastoma microRNA PRAS40 TGFβsignaling

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Neuroprotective effects of progesterone in acute brain trauma and its physiological mechanism

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Journal of Acute Disease 2018年第1期7卷 20-25页

作者： Luis Rafael Moscote-Salazar Alexis Narvaez-Rojas Amit Agrawal Guru Dutta Satyarthee Samer Hoz Johana Maraby-Salgado Andrei FJoaquim Cartagena neurotrauma Research Group Universidad de Cartagena CartagenaColombia Universidad Nacional Autonoma de Nicaragua Managua Cartagena Neurotrauma Research GroupUniversidad de CartagenaCartagenaColombia Department of Neurosurgery Narayna Medical College Hospital ChinthareddypalemNellore-524003Andhra PradeshIndia All India Institute of Medical Science New DelhiIndia Teaching Neurosurgery Hospital Bagdad-Iraq Universidad de Cartagena CartagenaColombia Department of Neurology Neurosurgery DivisionState University of CampinasCampinas-Sao PauloBrazil

Traumatic brain injury (TBI) is the leading cause of death and neurological disability in young adults worldwide. This work aims to review the role of progesterone in traumatic brain injury and the usefulness as a possible treatment. We searched pubmed database (2000-2017) for articles containing 'progesterone and brain traumatic injury'. Basic science studies have advanced knowledge of the mechanisms of secondary brain injury, creating prospects for the medical and pharmacological management of TBI. Although several comparative studies evaluated both the efficacy and safety of several groups of drugs, in which, corticosteroids, tranexamic acid, βreceptor antagonists, erythropoiesis-stimulating agents, reductase inhibitorsinclude hydroxymethyl glutaryl-CoA inhibitors (statins), among others. Several studies even evaluated the role of progesterone in the treatment of TBI, which is providing growing evidence about its potential neuroprotective mechanisms during the acute phase of trauma. Despite recent advances in the field of management of TBI care in the emergency units, intensive care and the multiple trials for more than 20 years to find useful pharmacological treatments, most of these efforts failed in pre-clinical stages (II and III).

关键词： Head trauma Progesterone Neural trauma Hormones

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Is more evidence needed for thrombectomy in basilar artery occlusion? The BASICS and BEST meta- analytical approaches

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Stroke & Vascular Neurology 2021年第4期6卷 671-672,I0094-I0096页

作者： Davi J Fontoura Solla Felipe Coelho Argolo Karol P Budohoski Angelos G Kolias JoséGuilherme M P Caldas Jamary Oliveira-Filho Division of Neurosurgery Department of NeurologyUniversity of Sao PauloSao PauloBrazil NIHR Global Health Research Group on neurotrauma Cambridge UniversityCambridgeUK Machine Learning for Mental Health Lab King's College LondonLondonUK Division of Neurosurgery Department of Clinical NeurosciencesAddenbrooke's HospitalCambridge UniversityCambridgeUK Radiology University of Sao PauloSao PauloBrazil Postgraduate Program in Health Sciences Federal University of BahiaSalvadorBahiaBrazil

INTRODUCTION The benefit of mechanical thrombectomy for stroke associated with anterior circulation large vessel occlusion(LVO)is well established and among the most effective treatments in medicine.1 Stroke associated with basilar artery occlusion(BAO)was not included in the seminal thrombectomy randomised clin-ical trials(RCTs).BAO accounts for 1%of the ischaemic strokes and 5%-10%of the LVO,but 70%-80%of BAO victims evolve to death or full dependence.23 The terminal nature of the brainstem and thalamic circulations may predispose to such dismal *** two RCT designed to assess the efficacy of early(<6-8 hours since symptoms onset)thrombectomy for BAO treatment,the BEST and BASICS trials.24 Given the prior evidence for thrombectomy benefit for anterior circu-lation stroke is well settled;BAO stroke shares a similar physiopathology with very poor prog-nosis.

关键词： throm occlusion basilar

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Exosomes from young healthy human plasma promote functional recovery from intracerebral hemorrhage via counteracting ferroptotic injury

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Bioactive Materials 2023年第9期27卷 1-14页

作者： Wenqin Yang Ning Ding Ran Luo Qian Zhang Zhenhua Li Fengchun Zhao Shuixian Zhang Xuyang Zhang Tengyuan Zhou Haomiao Wang Long Wang Shengli Hu Guixue Wang Hua Feng Rong Hu Department of Neurosurgery Key Laboratory of NeurotraumaSouthwest HospitalThird Military Medical University(Army Medical University)400038ChongqingChina Bioengineering College of Chongqing University Chongqing400030China Medical Research Center Southwest HospitalThird Military Medical University(Army Medical University)400038ChongqingChina Affiliated Dongguan Hospital Southern Medical UniversityDongguan523059China Key Laboratory of Biorheological and Technology of Ministry of Education State and Local Joint Engineering Laboratory for Vascular ImplantsBioengineering College of Chongqing UniversityChongqing400030China JinFeng Laboratory Chongqing401329China

Intracerebral hemorrhage (ICH), as a type of life-threatening and highly disabled disease, has limited therapeutic approaches. Here, we show that exosomes derived from young healthy human plasma exhibiting typical exosomes features could facilitate functional recovery of ICH mice. When these exosomes are intraventricularly delivered into the brain after ICH, they mainly distribute around the hematoma and could be internalized by neuronal cells. Strikingly, exosomes administration markedly enhanced the behavioral recovery of ICH mice through reducing brain injury and cell ferroptosis. MiRNA sequencing revealed that microRNA-25-3p (miR-25- 3p) was differentially expressed miRNA in the exosomes from young healthy human plasma, compared with exosomes from the old control. Importantly, miR-25-3p mimicked the treatment effect of exosomes on behavioral improvement, and mediated the neuroprotective effect of exosomes against ferroptosis in ICH. Furthermore, luciferase assay and western blotting data illustrated that P53 as assumed the role of a downstream effector of miR-25-3p, thereby regulating SLC7A11/GPX4 pathway to counteract ferroptosis. Taken together, these findings firstly reveal that exosomes from young healthy human plasma improve functional recovery through counteracting ferroptotic injury by regulating P53/SLC7A11/GPX4 axis after ICH. Given the easy availability of plasma exosomes, our study provides a potent therapeutic strategy for ICH patients with quick clinical translation in the near future.

关键词： Intracerebral hemorrhage Exosomes Young human plasma Ferroptosis Functional recovery

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Sepsis-induced mitochondrial dysfunction:A narrative review

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World Journal of Critical Care Medicine 2023年第3期12卷 139-152页

作者： Wagner Nedel Caroline Deutschendorf Luis Valmor Cruz Portela Intensive Care unit Grupo Hospitalar ConceiçãoPorto Alegre 91350200Brazil Laboratory of neurotrauma and Biomarkers Departamento de BioquímicaICBSUniversidade Federal do Rio Grande do SulPorto Alegre 90035-003Brazil Brazilian Research in Intensive Care Network-BRICNet São Paulo 04039-002Brazil Infection Control Committee Hospital de Clínicas de Porto AlegrePorto Alegre 90410-000Brazil

Sepsis represents a deranged and exaggerated systemic inflammatory response to infection and is associated with vascular and metabolic abnormalities that trigger systemic organic *** function has been shown to be severely impaired during the early phase of critical illness,with a reduction in biogenesis,increased generation of reactive oxygen species and a decrease in adenosine triphosphate synthesis of up to 50%.Mitochondrial dysfunction can be assessed using mitochondrial DNA concentration and respirometry assays,particularly in peripheral mononuclear *** of monocytes and lymphocytes seems to be the most promising strategy for measuring mitochondrial activity in clinical settings because of the ease of collection,sample processing,and clinical relevance of the association between metabolic alterations and deficient immune responses in mononuclear *** have reported alterations in these variables in patients with sepsis compared with healthy controls and non-septic ***,few studies have explored the association between mitochondrial dysfunction in immune mononuclear cells and unfavorable clinical *** improvement in mitochondrial parameters in sepsis could theoretically serve as a biomarker of clinical recovery and response to oxygen and vasopressor therapies as well as reveal unexplored pathophysiological mechanistic *** features highlight the need for further studies on mitochondrial metabolism in immune cells as a feasible tool to evaluate patients in intensive care *** evaluation of mitochondrial metabolism is a promising tool for the evaluation and management of critically ill patients,especially those with *** this article,we explore the pathophysiological aspects,main methods of measurement,and the main studies in this field.

关键词： Sepsis Mitochondria Mitochondrial dysfunction Oxidative phosphorylation Inflammation Respirometry

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