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Neuroprotection by cattle encephalon glycoside and ignotin beyond the time window of thrombolysis in ischemic stroke

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Neural Regeneration Research 2021年第2期16卷 312-318页

作者： Jun Zhong Rong-Wei Li Ju Wang Ying Wang Hong-Fei Ge Ji-Shu Xian Hua Feng Liang Tan department of Neurosurgery Southwest HospitalThe Third Military Medical University(Army Medical University)ChongqingChina department of Neurosurgery Hanzhong Central HospitalHanzhongShaanxi ProvinceChina department of Oncology Hanzhong Central HospitalHanzhongShaanxi ProvinceChina State key laboratory of Power Transmission Equipment and system Security and New Technology School of Electrical EngineeringChongqing UniversityChongqingChina

Cattle encephalon glycoside and ignotin(CEGI)injection is known as a multi-target neuroprotective drug that contains numerous liposoluble molecules,such as polypeptides,monosialotetrahexosyl ganglioside(GM-1),free amino acids,hypoxanthine and *** has been approved by the Chinese State Food and Drug Administration and widely used in the treatments of various diseases,such as stroke and Alzheimer's ***,the neuroprotective effects of CEGI beyond the time window of thrombolysis(within 4.5 hours)on acute ischemic stroke remain *** study constructed a rat middle cerebral artery occlusion model by suture-occluded method to simulate ischemic *** first daily dose was intraperitoneally injected at 8 hours post-surgery and the CEGI treatments continued for 14 *** of the modified five-point Bederson scale,beam balance test and rotameric test showed the neurological function of ischemic stroke rats treated with 4 m L/kg/d CEGI improved significantly,but the mortality within 14 days did not change *** MRI and 2,3,5-triphenyltetrazolium chloride staining confirmed that the infarct size in the 4 m L/kg/d CEGI-treated rats was significantly reduced compared with ischemic insult *** results of transmission electron microscopy and double immunofluorescence staining showed that the hippocampal neuronal necrosis in the ischemic penumbra decreased whereas the immunopositivity of new neuronal-specific protein doublecortin and the percentage of Ki67/doublecortin positive cells increased in CEGI-treated rats compared with untreated *** results suggest that CEGI has an effective neuroprotective effect on ischemic stroke when administered after the time window of *** study was approved by the Animal Ethics Committee of The Third Military Medical University,China.

关键词： apoptosis brain cattle encephalon glycoside and ignotin central nervous system neurological function plasticity rat regeneration stroke

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β-Receptor blocker enhances the anabolic effect of PTH after osteoporotic fracture

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Bone Research 2024年第2期12卷 302-313页

作者： Jie Huang Tong Wu Yi-Rong Jiang Xuan-Qi Zheng Huan Wang Hao Liu Hong Wang Hui-Jie Leng Dong-Wei Fan Wan-Qiong Yuan Chun-Li Song department of Orthopedics Peking University Third Hospital100191 BeijingChina beijing key laboratory of Spinal Disease 100191 BeijingChina Engineering Research Center of Bone and Joint Precision Medicine 100191 BeijingChina

The autonomic nervous system plays a crucial role in regulating bone metabolism,with sympathetic activation stimulating bone resorption and inhibiting bone *** found that fractures lead to increased sympathetic tone,enhanced osteoclast resorption,decreased osteoblast formation,and thus hastened systemic bone loss in ovariectomized(OVX)***,the combined administration of parathyroid hormone(PTH)and theβ-receptor blocker propranolol dramatically promoted systemic bone formation and osteoporotic fracture healing in OVX *** effect of this treatment is superior to that of treatment with PTH or propranolol *** vitro,the sympathetic neurotransmitter norepinephrine(NE)suppressed PTH-induced osteoblast differentiation and mineralization,which was rescued by ***,NE decreased the PTH-induced expression of Runx2 but enhanced the expression of Rankl and the effect of PTH-stimulated osteoblasts on osteoclastic differentiation,whereas these effects were reversed by ***,PTH increased the expression of the circadian clock gene Bmal1,which was inhibited by NE-βAR ***1 knockdown blocked the rescue effect of propranolol on the NE-induced decrease in PTHstimulated osteoblast *** together,these results suggest that propranolol enhances the anabolic effect of PTH in preventing systemic bone loss following osteoporotic fracture by blocking the negative effects of sympathetic signaling on PTH anabolism.

关键词： blocker metabolism inhibited

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Expert consensus on drug treatment of chronic subdural hematoma

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Chinese Neurosurgical Journal 2022年第1期8卷 51-59页

作者： Jianning Zhang Chinese Society of Neurosurgery Chinese Medical Association Chinese Neurosurgical Critical Care Specialist Council Collaborational Group of Chinese Neurosurgical Translational and Evidence-based Medicine department of Neurosurgery Tianjin Medical University General HospitalTianjin 300052China key laboratory of Post-trauma Neuro-repair and Regeneration in central nervous system Ministry of EducationTianjin 300052China Tianjin key laboratory of Injuries Variations and Regeneration of Nervous SystemTianjin 300052China Tianjin Neurological Institute Tianjin 300052China 不详

Chronic subdural hematoma(CSDH)is a chronic space-occupying lesion formed by blood accumulation between arachnoid and dura mater,which is usually formed in the third week after traumatic brain *** treatment is usually the first choice for patients with CSDH having a significant space-occupying *** of the patients showed good results of surgical treatment,but still some patients had a postoperative recurrence(the recurrence rate was up to 33%).Because CSDH is often seen in the elderly,patients are weak and have many basic *** risk of surgical treatment is high;serious complications and even death(the death rate is up to 32%)can often *** overall good prognosis rate of patients aged more than 90 years is 24%.The drug treatment can provide a safe and effective treatment for elderly patients who are weak,intolerable to surgery,or failed in ***-dose and long-term use of atorvastatin(20mg/d)is suggested for continuous treatment for at least 8 weeks,while low-dose and short-term use of dexamethasone can improve the therapeutic effect of atorvastatin on *** should undergo CT or MRI scanning at least one time within 2 weeks after the start of drug treatment.

关键词： CSDH treatment drug death

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The lymphatic system:a therapeutic target for central nervous system disorders

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Neural Regeneration Research 2023年第6期18卷 1249-1256页

作者： Jia-Qi Xu Qian-Qi Liu Sheng-Yuan Huang Chun-Yue Duan Hong-Bin Lu Yong Cao Jian-Zhong Hu department of Spine Surgery and Orthopaedics Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina key laboratory of Organ injury Aging and Regenerative Medicine of Hunan ProvinceChangshaHunan ProvinceChina Mobile Health Ministry of Education-China Mobile Joint laboratory ChangshaHunan ProvinceChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina department of Cardiovascular Surgery The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina department of Sports Medicine Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

The lymphatic vasculature forms an organized network that covers the whole body and is involved in fluid homeostasis,metabolite clearance,and immune *** recent identification of functional lymphatic vessels in the meninges of the brain and the spinal cord has provided novel insights into *** emerge as major pathways for fluid *** abundance of immune cells in lymphatic vessels and meninges also suggests that lymphatic vessels are actively involved in *** lymphatic system,through its role in the clearance of neurotoxic proteins,autoimmune cell infiltration,and the transmission of pro-inflammatory signals,participates in the pathogenesis of a variety of neurological disorders,including neurodegenerative and neuroinflammatory diseases and traumatic *** endothelial growth factor C is the master regulator of lymphangiogenesis,a process that is critical for the maintenance of central nervous system *** this review,we summarize current knowledge and recent advances relating to the anatomical features and immunological functions of the lymphatic system of the central nervous system and highlight its potential as a therapeutic target for neurological disorders and central nervous system repair.

关键词： central nervous system central nervous system injury glymphatic system lymphatic vessels meninges neurodegenerative disorders neuroinflammatory diseases vascular endothelial growth factor C

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Cortical plasticity and nerve regeneration after peripheral nerve injury

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Neural Regeneration Research 2021年第8期16卷 1518-1523页

作者： Ci Li Song-Yang Liu Wei Pi Pei-Xun Zhang department of Orthopedics and Trauma Peking University People’s HospitalBeijingChina key laboratory of Trauma and Neural Regeneration Peking UniversityBeijingChina National Center for Trauma Medicine BeijingChina

With the development of neuroscience, substantial advances have been achieved in peripheral nerve regeneration over the past decades. However, peripheral nerve injury remains a critical public health problem because of the subsequent impairment or absence of sensorimotor function. Uncomfortable complications of peripheral nerve injury, such as chronic pain, can also cause problems for families and society. A number of studies have demonstrated that the proper functioning of the nervous system depends not only on a complete connection from the central nervous system to the surrounding targets at an anatomical level, but also on the continuous bilateral communication between the two. After peripheral nerve injury, the interruption of afferent and efferent signals can cause complex pathophysiological changes, including neurochemical alterations, modifications in the adaptability of excitatory and inhibitory neurons, and the reorganization of somatosensory and motor regions. This review discusses the close relationship between the cerebral cortex and peripheral nerves. We also focus on common therapies for peripheral nerve injury and summarize their potential mechanisms in relation to cortical plasticity. It has been suggested that cortical plasticity may be important for improving functional recovery after peripheral nerve damage. Further understanding of the potential common mechanisms between cortical reorganization and nerve injury will help to elucidate the pathophysiological processes of nerve injury, and may allow for the reduction of adverse consequences during peripheral nerve injury recovery. We also review the role that regulating reorganization mechanisms plays in functional recovery, and conclude with a suggestion to target cortical plasticity along with therapeutic interventions to promote peripheral nerve injury recovery.

关键词： cortical plasticity injury mechanisms nerve transfer neurorrhaphy peripheral nerve phantom limb pain recovery regeneration treatment

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Inhibiting ceramide synthase 5 expression in microglia decreases neuroinflammation after spinal cord injury

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Neural Regeneration Research 2025年第10期20卷 2955-2968页

作者： Wei Zhang Yubao Lu Ruoqi Shen Yingjie Wu Chenrui Liu Xingxing Fang Liangming Zhang Bin Liu Limin Rong department of Spine Surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina National Medical Products Administration(NMPA)key laboratory for Quality Research and Evaluation of Cell Products GuangzhouGuangdong ProvinceChina Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery GuangzhouGuangdong ProvinceChina Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery GuangzhouGuangdong ProvinceChina

Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord ***,the precise mechanism remains *** investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial *** found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high ***,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord ***,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron *** ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced ***,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling *** ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological ***2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling ***,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.

关键词： ceramide synthase 5 gasdermin D microglia neuroinflammation NLRP3 nuclear factor kappa B Pla2g7 pyroptosis sphingomyelin metabolism spinal cord injury

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Immune checkpoint inhibitors in malignant lymphoma: Advances and perspectives

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Chinese Journal of Cancer Research 2020年第3期32卷 303-318页

作者： Ningjing Lin Yuqin Song Jun Zhu key laboratory of Carcinogenesis and Translational Research(Ministry of Education/beijing) Department of LymphomaPeking University Cancer Hospital&InstituteBeijing 100142China

Classical Hodgkin lymphoma(cHL) has been identified with universal genetic alterations of chromosome 9p24.1,which contains PD-L1/PD-L2 *** amplification of 9p24.1 is associated with the increased expression of PDL1 and PD-L2 on RS cells, which promotes their immune evasion, and subsequently makes cHL sensitive to PD-1 *** PD-1 inhibitors have shown significant efficacies with overall response rate(ORR) of 70%-90% in relapse/refractory(r/r) cHL and have acquired the approvals for this ***, more and more studies are conducted to investigate PD-1 blockade in earlier disease course and in combination with neo-agents or *** cHL, non-Hodgkin lymphoma(NHL) consists of numerous subtypes harboring highly biological *** a few subtypes have been shown to have genetic alteration of 9p24.1 including primary mediastinal B cell lymphoma(PMBL), gray zone lymphoma(GZL) with features intermediate between diffuse large B cell lymphoma(DLBCL) and cHL, primary central nervous system lymphoma(PCNSL) and primary testicular lymphoma(PTL).Epstein-Barr virus(EBV)-associated lymphomas have a virally mediated overexpression of PD-L1, also making them sensitive to PD-1 ***, PD-1 inhibitors are less effective in most r/r NHL than in r/r *** understanding of the biological features of NHL and immune checkpoint inhibitors(ICPi) combined therapy is the research focus in the *** this review, we outlined the recent progress of ICPi in lymphoma originating from clinical studies.

关键词： Immunotherapy immune checkpoint inhibitor PD-1 blockade Hodgkin lymphoma non-Hodgkin lymphoma

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Electroporation Transfection as an Effective Tool to Trace Transplanted NSCs in Adult central nervous system

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Tsinghua Science and Technology 2004年第1期9卷 81-87页

作者：周畅温哲鈃王志萍郭行史冬梅左焕琮谢佐平 State key laboratory of Biomembrane and Membrane Biotechnology Department of Biological Sciences and Biotechnology Tsinghua University Beijing 100084 China

Neural stem cells, which are clonogenic cells with self-renewal and multilineage differentiation properties, are currently considered as powerful candidates for cell replacement therapy in neurodegenerative disorders such as Parkinson's disease. A key issue is whether stem cells can survive, migrate and differentiate following transplantation into the adult central nervous system. This research shows that enhanced green fluorescent protein (EGFP) plasmid electroporation transfected neural stem cells can functionally differentiate in vitro and that most of the EGFP-positive cells can survive and migrate towards the damaged areas when transplanted into the brain of a Parkinson抯 disease model rat. The results suggest an effective and maneuverable tracing tool to detect whether transplanted neural stem and progenitor cells function in the adult brain in vivo.

关键词： neural stem cell electroporation transfection enhanced green fluorescent protein transplantation migrate

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Local delivery of EGFR+NSCs-derived exosomes promotes neural regeneration post spinal cord injury via miR-34a-5p/HDAC6 pathway

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Bioactive Materials 2024年第3期33卷 424-443页

作者： Tian Qin Chengjun Li Yan Xu Yiming Qin Yuxin Jin Rundong He Zixiang Luo Jinyun Zhao Chunyue Duan Hongbin Lu Yong Cao Jianzhong Hu department of Spine Surgery and Orthopaedics Xiangya HospitalCentral South UniversityXiangya Road 87Changsha410008China key laboratory of Organ injury Aging and Regenerative Medicine of Hunan ProvinceXiangya Road 87Changsha410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityXiangya Road 87Changsha410008China department of Sports Medicine Xiangya HospitalCentral South UniversityXiangya Road 87Changsha410008China

Spinal cord injury(SCI)causes severe axon damage,usually leading to permanent paraparesis,which still lacks effective regenerative *** studies have suggested that exosomes derived from neural stem cells(NSCs)may hold promise as attractive candidates for SCI *** Growth Factor Receptor positive NSC(EGFR+NSC)is a subpopulation of endogenous NSCs,showing strong regenerative capability in central nervous system *** the current study,we isolated exosomes from the EGFR+NSCs(EGFR+NSCs-Exos)and discovered that local delivery of EGFR+NSCs-Exos can effectively promote neurite regrowth in the injury site of spinal cord-injured mice and improve their neurological function *** the miRNA-seq,we firstly characterized the microRNAs(miRNAs)cargo of EGFR+NSCs-Exos and identified miR-34a-5p which was highly enriched in EGFR+NSCs derived *** further interpreted that exosomal miR-34a-5p could be transferred to neurons and inhibit the HDAC6 expression by directly binding to its mRNA,contributing to microtubule stabilization and autophagy induction for aiding SCI ***,our research demonstrated a novel therapeutic approach to improving neurological functional recovery by using exosomes secreted from a subpopulation of endogenous NSCs and providing a precise cell-free treatment strategy for SCI repair.

关键词： Spinal cord injury Exosomes Neural regeneration miR-34a-5p HDAC6

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Antisense MMP-9 RNA inhibits malignant glioma cell growth in vitro and in vivo

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Neuroscience Bulletin 2013年第1期29卷 83-93页

作者： Cuiyun Sun Qian Wang Hongxu Zhou Shizhu Yu Alain R. Simard Chunsheng Kang Yanyan Li Yanling Kong Tongling An Yanjun Wen Fudong Shi Junwei Hao department of Neuropathology Tianjin Neurological Institute Tianjin Medical University General Hospital key laboratory of Post-trauma Neuro-repair and Regeneration in the central nervous system Ministry of Education Tianjin key laboratory of Injuries Variations and Regeneration of the Nervous System Département de Chimie et Biochimie Université de Moncton Moncton New Brunswick E1A 3E9 Canada department of Neurology Tianjin Neurological Institute Tianjin Medical University General Hospital

The matrix-degrading metalloproteinases （MMPs）, particularly MMP-9, play important roles in the pathogenesis and development of malignant gliomas. In the present study, the oncogenic role of MMP-9 in malignant glioma cells was investigated via antisense RNA blockade in vitro and in vivo. TJ905 malignant glioma cells were transfected with pcDNA3.0 vector expressing antisense MMP-9 RNA （pcDNA-AS-MMP9）, which significantly decreased MMP-9 expression, and cell proliferation was assessed. For in vivo studies, U251 cells, a human malignant glioma cell line, were implanted subcutaneously into 4-to 6-week-old BALB/c nude mice. The mice bearing well-established U251 gliomas were treated with intratumoral pcDNA-AS-MMP9-Lipofectamine complex （AS-MMP-9-treated group）, subcutaneous injection of endostatin （endostatin-treated group）, or both （combined therapy group）. Mice treated with pcDNA （empty vector）-Lipofectamine served as the control group. Four or eight weeks later, the volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity were assayed. We demonstrate that pcDNA-AS-MMP9 significantly decreased MMP-9 expression and inhibited glioma cell proliferation. Volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity in the antisense-MMP-9-treated and therapeutic alliance groups were significantly lower than those in the control group. The results suggest that MMP-9 not only promotes malignant glioma cell invasiveness, but also affects tumor cell proliferation. Blocking the expression of MMP-9 with antisense RNA substantially suppresses the malignant phenotype of glioma cells, and thus can be used as an effective therapeutic strategy for malignant gliomas.

关键词： matrix-degrading metalloproteinase 9 antisense MMP-9 RNA cell proliferation malignant glioma cells

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