Mechanisms of Preferential Reinveration
优先再反转机制
基本信息
- 批准号:8437171
- 负责人:
- 金额:$ 33.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-04-01 至 2014-03-31
- 项目状态:已结题
- 来源:
- 关键词:AmericanAnimal ModelAxonClinicalComplexCutaneousCutaneous MuscleDistalElectroporationEnzyme-Linked Immunosorbent AssayGene ExpressionGoalsGrowthGrowth FactorGrowth Factor GeneHealthIn VitroIndividualKnowledgeLaboratoriesLentivirus VectorMeasuresModalityModelingMotorMotor PathwaysMuscleNatural regenerationNerveNerve RegenerationOperative Surgical ProceduresOutcomePatientsPatternPerformancePeripheral NervesPhenotypePopulationProcessProductionRattusRecoveryRecovery of FunctionRegression AnalysisResearchSchwann CellsSensorySpecificitySpeedTechniquesTissue-Specific Gene ExpressionTubeUpper ExtremityVentral RootsViralWorkaxon regenerationbasefunctional outcomesimprovedin vivomedian nervemeetingsnerve injurynovelplasmid DNAreconstructionreinnervationrelating to nervous systemrepairedresearch studyrestorationspinal cord regenerationspinal nerve posterior root
项目摘要
DESCRIPTION (provided by applicant): Nerve injury compromises the function of over 80,000 Americans each year. Surprisingly, the treatment of nerve injury, surgical restoration of gross nerve continuity, has changed little in the last century. The discovery of factors that promote nerve regeneration has stimulated experimentation in a variety of animal models. In spite of this promising work, however, we still lack precise knowledge of which factors promote the regeneration of specific axon populations in vivo. This proposal extends work ongoing in our laboratory to provide this knowledge. We have shown that Schwann cells of myelinating peripheral nerve, once thought to express a single phenotype, vary widely in their growth factor expression. Furthermore, these specialized Schwann cells preferentially support the regeneration of their native axon population. We now propose to determine which of the factors expressed differentially in sensory and motor nerve are responsible for selective promotion of sensory and motor axon regeneration. Analysis will begin with correlation of growth factor concentration in various types of graft with their ability to promote sensory or motor regeneration. We have devised a novel technique of nerve repair in vitro that closely mimics repair in vivo, and will use this to observe the effects of augmenting or eliminating the function of specific factors. Schwann cells will then be modified in vivo to increase the expression of promising factors by transfecting them with lentiviral vectors or electroporating them with DNA plasmids. The most effective growth factors will be evaluated in the rat median nerve by measuring their impact on recovery of patterned and voluntary function after nerve grafting. Identification of the specific factors needed for optimal sensory and motor axon regeneration will have direct and immediate clinical implications for nerve repair, nerve grafting, and the use of Schwann cells to promote spinal cord regeneration.
描述(由申请人提供):神经损伤损害每年超过80,000美国人的功能。令人惊讶的是,神经损伤的治疗,手术恢复大体神经连续性,在上个世纪几乎没有变化。促进神经再生的因素的发现刺激了各种动物模型的实验。尽管这项工作很有前途,但是,我们仍然缺乏确切的知识,哪些因素促进再生的特定轴突群体在体内。这项建议扩展了我们实验室正在进行的工作,以提供这方面的知识。我们已经表明,髓鞘周围神经的许旺细胞,一旦被认为是表达一个单一的表型,在他们的生长因子表达的差异很大。此外,这些特化的许旺细胞优先支持其天然轴突群的再生。我们现在建议确定哪些因素差异表达的感觉和运动神经负责选择性促进感觉和运动轴突再生。分析将开始于各种类型移植物中生长因子浓度与其促进感觉或运动再生能力的相关性。我们已经设计了一种新的体外神经修复技术,它可以很好地模拟体内修复,并将利用这种技术来观察增强或消除特定因子功能的效果。然后,通过用慢病毒载体转染或用DNA质粒电穿孔,在体内修饰雪旺细胞以增加有希望的因子的表达。将通过测量它们对神经移植后模式和随意功能恢复的影响,在大鼠正中神经中评价最有效的生长因子。识别最佳感觉和运动轴突再生所需的特定因素将对神经修复、神经移植和使用雪旺细胞促进脊髓再生具有直接和立即的临床意义。
项目成果
期刊论文数量(20)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Schwann cell phenotype is regulated by axon modality and central-peripheral location, and persists in vitro.
- DOI:10.1016/j.expneurol.2013.05.007
- 发表时间:2013-09
- 期刊:
- 影响因子:5.3
- 作者:Brushart TM;Aspalter M;Griffin JW;Redett R;Hameed H;Zhou C;Wright M;Vyas A;Höke A
- 通讯作者:Höke A
An in vitro model of adult mammalian nerve repair.
- DOI:10.1016/j.expneurol.2009.05.022
- 发表时间:2010-05
- 期刊:
- 影响因子:5.3
- 作者:Vyas, Alka;Li, Zhaobo;Aspalter, Manuela;Feiner, Jeffrey;Hoke, Ahmet;Zhou, Chunhua;O'Daly, Andres;Abdullah, Madeel;Rohde, Charles;Brushart, Thomas M.
- 通讯作者:Brushart, Thomas M.
Rolipram-induced elevation of cAMP or chondroitinase ABC breakdown of inhibitory proteoglycans in the extracellular matrix promotes peripheral nerve regeneration.
咯利普兰诱导的 cAMP 升高或细胞外基质中抑制性蛋白聚糖的软骨素酶 ABC 分解可促进周围神经再生。
- DOI:10.1016/j.expneurol.2009.08.026
- 发表时间:2010
- 期刊:
- 影响因子:5.3
- 作者:Udina,E;Ladak,A;Furey,M;Brushart,T;Tyreman,N;Gordon,T
- 通讯作者:Gordon,T
A two-compartment organotypic model of mammalian peripheral nerve repair.
- DOI:10.1016/j.jneumeth.2014.05.005
- 发表时间:2014-07-30
- 期刊:
- 影响因子:3
- 作者:Siddique, Rezina;Vyas, Alka;Thakor, Nitish;Brushart, Thomas M.
- 通讯作者:Brushart, Thomas M.
The topographic specificity of muscle reinnervation predicts function.
肌肉神经支配的地形特异性可预测功能。
- DOI:10.1111/ejn.13058
- 发表时间:2016
- 期刊:
- 影响因子:0
- 作者:O'Daly,Andres;Rohde,Charles;Brushart,Thomas
- 通讯作者:Brushart,Thomas
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
THOMAS M BRUSHART其他文献
THOMAS M BRUSHART的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('THOMAS M BRUSHART', 18)}}的其他基金
Harnessing Neurotropism to Sort Sensory and Motor Axons
利用向神经性对感觉和运动轴突进行分类
- 批准号:
9765432 - 财政年份:2018
- 资助金额:
$ 33.93万 - 项目类别:
MOTOR/SENSORY SPECIFICITY--MECHANISMS AND AUGMENTATION
运动/感觉特异性——机制和增强
- 批准号:
6339902 - 财政年份:1997
- 资助金额:
$ 33.93万 - 项目类别:
MOTOR/SENSORY SPECIFICITY--MECHANISMS AND AUGMENTATION
运动/感觉特异性——机制和增强
- 批准号:
2038038 - 财政年份:1997
- 资助金额:
$ 33.93万 - 项目类别:
相似海外基金
Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
- 批准号:
495434 - 财政年份:2023
- 资助金额:
$ 33.93万 - 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
- 批准号:
10642519 - 财政年份:2023
- 资助金额:
$ 33.93万 - 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
- 批准号:
10586596 - 财政年份:2023
- 资助金额:
$ 33.93万 - 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
- 批准号:
10590479 - 财政年份:2023
- 资助金额:
$ 33.93万 - 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
- 批准号:
23K06011 - 财政年份:2023
- 资助金额:
$ 33.93万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
- 批准号:
10682117 - 财政年份:2023
- 资助金额:
$ 33.93万 - 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
- 批准号:
10708517 - 财政年份:2023
- 资助金额:
$ 33.93万 - 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
- 批准号:
10575566 - 财政年份:2023
- 资助金额:
$ 33.93万 - 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
- 批准号:
23K15696 - 财政年份:2023
- 资助金额:
$ 33.93万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
- 批准号:
23K15867 - 财政年份:2023
- 资助金额:
$ 33.93万 - 项目类别:
Grant-in-Aid for Early-Career Scientists