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Epidural electrical stimulation for spinal cord injury

Neural Regeneration Research 2021年第12期16卷 2367-2375页

作者： Elliot H.Choi Sandra Gattas Nolan J.Brown John D.Hong Joshua N.Limbo Alvin y.Chan michael y.oh Department of Pharmacology School of MedicineCase Western Reserve UniversityClevelandOHUSA Department of Ophthalmology Gavin Herbert Eye InstituteSchool of MedicineUniversity of CaliforniaIrvineCAUSA Department of Neurosurgery University of CaliforniaIrvineCAUSA

A long-standing goal of spinal cord injury research is to develop effective repair strategies,which can restore motor and sensory functions to near-normal *** advances in clinical management of spinal cord injury have significantly improved the prognosis,survival rate and quality of life in patients with spinal cord *** addition,a significant progress in basic science research has unraveled the underlying cellular and molecular events of spinal cord *** efforts enabled the development of pharmacologic agents,biomaterials and stem-cell based *** these efforts,there is still no standard care to regenerate axons or restore function of silent axons in the injured spinal *** challenges led to an increased focus on another therapeutic approach,namely *** multiple animal models of spinal cord injury,epidural electrical stimulation of the spinal cord has demonstrated a recovery of motor *** evidence regarding the efficacy of epidural electrical stimulation has further expanded the potential of epidural electrical stimulation for treating patients with spinal cord ***,most clinical studies were conducted on a very small number of patients with a wide range of spinal cord ***,subsequent studies are essential to evaluate the therapeutic potential of epidural electrical stimulation for spinal cord injury and to optimize stimulation ***,we discuss cellular and molecular events that continue to damage the injured spinal cord and impede neurological recovery following spinal cord *** also discuss and summarize the animal and human studies that evaluated epidural electrical stimulation in spinal cord injury.

关键词： central nervous system chondroitin sulfate proteoglycans epidural electrical stimulation glial scar gliosis neural activity neuromodulation oligodendrocyte spinal cord injury

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Therapeutic potential of neuromodulation for demyelinating diseases

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Neural Regeneration Research 2021年第2期16卷 214-217页

作者： Elliot H.Choi Chioma Nwakalor Nolan J.Brown Joonho Lee michael y.oh In Hong yang Department of Pharmacology School of MedicineCase Western Reserve UniversityClevelandOHUSA Department of Ophthalmology Gavin Herbert Eye InstituteSchool of MedicineUniversity of CaliforniaIrvineCAUSA Department of Neurological Surgery University of CaliforniaIrvineCAUSA Department of Mechanical Engineering and Engineering Science Center for Biomedical Engineering and ScienceUniversity of North Carolina at CharlotteCharlotteNCUSA University of Rochester School of Medicine and Dentistry RochesterNYUSA

Neuromodulation represents a cutting edge class of both invasive and non-invasive therapeutic methods which alter the activity of ***,several different techniques have been developed-or are currently being investigated–to treat a wide variety of neurological and neuropsychiatric ***,in vivo and in vitro studies have revealed that neuromodulation can also induce myelination,meaning that it could hold potential as a therapy for various demyelinating diseases including multiple sclerosis and progressive multifocal *** findings come on the heels of a paradigm shift in the view of myelin's role within the nervous system from a static structure to an active co-regulator of central nervous system plasticity and participant in neuron-mediated *** the present review,we highlight several of the recent findings regarding the role of neural activity in altering myelination including several soluble and contact-dependent factors that seem to mediate neural activitydependent *** also highlight several considerations for neuromodulatory techniques,including the need for further research into spatiotemporal precision,dosage,and the safety and efficacy of transcranial focused ultrasound stimulation,an emerging neuromodulation *** the field of neuromodulation continues to evolve,it could potentially bring forth methods for the treatment of demyelinating diseases,and as such,further investigation into the mechanisms of neuron-dependent myelination as well as neuro-imaging modalities that can monitor myelination activity is warranted.

关键词： central nervous system deep brain stimulation myelination neural activity oligodendrocyte optogenetic stimulation transcranial electrical stimulation transcranial focused ultrasound stimulation transcranial magnetic stimulation

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Like a G6-nal:transcriptional control of G-protein coupled receptors during oligodendroglial development

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Neural Regeneration Research 2025年第7期20卷 2001-2002页

作者： Tim Aberle michael Wegner Institut für Biochemie Friedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany

Multilayered control of myelination:Quick,saltatory conduction of action potentials along nerve fibers requires the electrical insulation of axons by myelinating *** the central nervous system,this role is taken up by *** are marked by the expression of the lineage determinants Sox10 and Olig2 and arise from oligodendrocyte precursor cells(OPCs)during embryonal *** the majority of OPCs differentiate into mature oligodendrocytes when nearby axonal segments require myelination,a small subpopulation of OPCs persist as a progenitor ***,the timing of myelination and maintenance of the OPC pool both need to be precisely *** transcription factors either positively or negatively affect oligodendrocyte differentiation and maintenance of the OPC pool as components of a complex gene regulatory network(reviewed in Sock and Wegner,2021).Network activity is additionally influenced by extracellular signaling molecules that bind to receptors on the oligodendroglial cell surface and activate intracellular signaling *** the receptors are linked to the network is poorly understood so far,but pivotal to understanding the overall regulation of central nervous system(CNS)myelination in response to environmental *** insights were recently gained for Gpr37(Schmidt et al.,2024),a G-protein coupled receptor(GPCR)with known relevance in differentiating oligodendrocytes(yang et al,2016).

关键词： gained insulation conduction

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Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 174-180页

作者： yinglong Miao michael S.Wolfe Computational Medicine Program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-Secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-Stay-Trim,”“Sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

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NECAB family of neuronal calcium-binding proteins in health and disease

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Neural Regeneration Research 2025年第5期20卷 1236-1243页

作者： Diones Bueno michael K.E.Schafer Sudena Wang michael J.Schmeisser Axel Methner Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Department of Anesthesiology University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Institute of Anatomy University Medical Center of the Johannes Gutenberg-UniversityMainzGermany

The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interac

关键词： calcium EF hand mitochondria nervous system signal transduction

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静电纺嵌锰聚丙烯腈基活性碳纳米纤维及其甲苯吸附性表征

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合成纤维 2008年第10期37卷 49-53页

作者： G.-y.oh 刘呈坤

利用分散有不同锰含量的聚丙烯腈(PAN)混合溶液,通过静电纺制备聚合物纤维,然后经过预氧化、碳化和活化工艺对静电纺获得的聚合物纤维进行处理以合成活性碳纳米纤维。活化工艺如下:氮气气氛下,于体积比为30%的蒸汽(800℃)中处理30 min... 详细信息

利用分散有不同锰含量的聚丙烯腈(PAN)混合溶液,通过静电纺制备聚合物纤维,然后经过预氧化、碳化和活化工艺对静电纺获得的聚合物纤维进行处理以合成活性碳纳米纤维。活化工艺如下:氮气气氛下,于体积比为30%的蒸汽(800℃)中处理30 min。不含锰或者嵌锰的活性碳纳米纤维的平均直径约为250 nm。从对孔表征的结果可以看出,具有更高比表面积以及更大孔容的活性碳纳米纤维在甲苯的吸附中占据优势,不含锰的样品的甲苯吸附能力为40 g甲苯/100 g活性碳纳米纤维,然而,嵌有0.23%锰的样品的甲苯吸附能力为68 g甲苯/100 g复合碳纳米纤维,其对应的比表面积、微孔容以及平均微孔直径分别为1229 m2/g、0.416 cm3/g和5.8魡。适合于甲苯吸附的微孔特征是由静电纺、锰粒子的添加以及活化工艺进行控制,这是为什么要通过静电纺制备定向排列和锰(用于作为催化反应的催化剂)分散良好的纳米纤维,以及寻求最佳活化条件防止产生中孔的原因。对于活性碳纳米纤维的表面化学性能,所有样品表面的氧/碳比(O/C)是相似的(约为0.1),这表明活性碳纳米纤维表面是非极性的。

关键词：碳纳米纤维合成活性聚丙烯腈基锰含量静电纺吸附性甲苯表征

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Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

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Neural Regeneration Research 2025年第1期20卷 224-233页

作者： yi Zhang Zhongwu Liu michael Chopp michael Millman yanfeng Li Pasquale Cepparulo Amy Kemper Chao Li Li Zhang Zheng Gang Zhang Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA Department of Pathology Henry Ford HospitalDetroitMIUSA Division of Pharmacology Department of NeuroscienceReproductive and Dentistry SciencesSchool of MedicineUniversity of Naples“Federico Ⅱ”NaplesItaly

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional *** previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic *** the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression *** EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a *** male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or *** array of behavior assays was used to measure neurological *** with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological *** vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal *** analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct *** of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of *** data provide evidence that 27a-sEVs have

关键词： axonal remodeling cerebral endothelial cells exosomes miR-27a mitochondria Semaphorin 6A small extracellular vesicles stroke

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Cortical hem signaling center: functions, development, and potential implications for evolution and brain disorders

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Neural Regeneration Research 2025年第4期20卷 1079-1080页

作者： Victor V.Chizhikov Igor y.Iskusnykh Department of Anatomy and Neurobiology University of Tennessee Health Science CenterMemphisTNUSA

Development of the telencephalon relies upon several signaling centers-localized cellular populations that supply secreted factors to pattern the cortical *** such signaling center is the cortical hem,which arises during embryonic development at the telencephalic dorsal midline,adjacent to the choroid plexus and hippocampal primordium(Figure 1A).While the cortical hem has also been described in reptiles and birds,most of our knowledge about the developmental roles of the cortical hem is derived from the analysis in *** cortical hem produces several types of secreted molecules,including wingless-related integration site(Wnt)and bone morphogenetic(Bmp)*** cortical hem is particularly important for the development of the hippocampus,which is involved in learning and memory,and the neocortex,which is the most complex brain region that mediates multiple types of behavior and higher cognitive functions(Mangale et al.,2008;Dal-Valle-Anton and Borrell,2022).

关键词： epithelium Figure center

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Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

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Neural Regeneration Research 2025年第7期20卷 1981-1988页

作者： Shan Ping yu Emily Choi michael QJiang Ling Wei Department of Anesthesiology Emory University School of MedicineAtlantaGAUSA Center for Visual and Neurocognitive Rehabilitation Atlanta Veterans Affairs Medical CenterDecaturGAUSA

Stroke and Alzheimer's disease are common neurological disorders and often occur in the same *** comorbidity of the two neurological disorders represents a grave health threat to older *** review presents a brief background of the development of novel concepts and their clinical *** activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal *** ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic *** Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute ***,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death *** on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic *** N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic *** stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time *** is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related

关键词： Ca^(2+)hypothesis cognitive deficits hyperactivity late-onset Alzheimer's disease neurodegeneration N-methyl-D-aspartate receptors N-methyl-D-aspartate receptor subunits pathogenesis preventive treatment

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In-situ production of ozone and ultraviolet light using a barrier discharge reactor for wastewater treatment

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2009年第9期10卷 1359-1366页

作者： Jin-oh JO y.S.MOK Department of Chemical and Biological Engineering Jeju National University

A dielectric barrier discharge (DBD) reactor consisting of water-filled dielectric tube electrodes was used for the treatment of wastewater. The inner dielectric tube, which acted as the discharging electrode, was filled with an aqueous electrolyte solution. The outer dielectric tube, which served as the other electrode, was in contact with the wastewater, which was grounded. The present reactor system was energy-efficient for the production of ozone, not only because the perfect contact between the aqueous electrode and the dielectric surface minimized the loss of the electrical energy, but also because the DBD reactor was cooled by the wastewater. In addition, the ultraviolet (UV) light produced in the DBD reactor was able to assist in the wastewater treatment since the quartz tube used as the dielectric material was UV-transparent. The performance of the present DBD system was evaluated using a synthetic wastewater formed from distilled water and an azo dye, amaranth. The experimental parameters were the concentration of the electrolyte in the aqueous electrode, the discharge power, the initial pH of the wastewater and the concentration of hydrogen peroxide added to the wastewater. The wastewater treatment system was found to be effective for achieving decomposition of the dye.

关键词： Dielectric barrier discharge (DBD) Aqueous electrode Ozone Ultraviolet (UV) Wastewater

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