Spinal Neuromodulation to Promote Physiologic and Molecular Plasticity in theInjured Spinal Cord
脊髓神经调节促进受损脊髓的生理和分子可塑性
基本信息
- 批准号:10805726
- 负责人:
- 金额:$ 46.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-20 至 2028-08-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAnatomyAnimal ExperimentsAnimalsAreaBiologyCervicalCervical spinal cord injuryCervical spinal cord structureChronicClinicalClinical DataClinical ResearchContusionsDataDevicesDorsalDoseEffectivenessElectric StimulationElectrodesEngineeringFamilyFiberForelimbFutureGene ExpressionGenetic TranscriptionHourInformaticsInjuryInvestigationLesionLocomotionMapsMethodsModelingMolecularMotorMuscleNeuronal PlasticityParalysedPathway interactionsPatientsPatternPerformancePersonsPhysiologicalPhysiologyPositioning AttributePublishingQuadriplegiaQuality of lifeRattusRecoveryRecovery of FunctionRehabilitation therapyReportingResearchRetinal blind spotRodentRoleSensorySiteSpeedSpinalSpinal CordSpinal cord injuryStrokeSurfaceTestingTimeTrainingTraumatic Brain InjuryUpper ExtremityVertebral columnWalkingWorkcandidate identificationcentral pattern generatorclinically relevantcostexperienceexperimental studyfunctional improvementfunctional plasticitygene regulatory networkhand rehabilitationimprovedinnovationinsightinterestintraspinal microstimulationmotor recoverynerve injuryneuralneuroinflammationneuroregulationnovelnovel strategiespre-clinicalrestorationtranscriptomics
项目摘要
Abstract
There is growing interest in the use of electrical stimulation to promote the recovery of sensorimotor and
autonomic function after neural injury. Previous research from our lab and others has demonstrated that
stimulation of spinal lumbar segments activates central pattern generators, which, in turn, facilitates standing
and walking. However, while there is extensive animal, pre-clinical, and clinical data examining the impact of
lumbar stimulation, studies that apply neuromodulation to the cervical spinal cord for upper limb are very limited.
Here, we propose that fundamental blind spots exist in the field of neuromodulation for upper limb, including
where to stimulate anatomically, how to dose and, especially, mechanisms of action. The Horner lab has
developed a clinically relevant rat model of cervical spinal cord injury and engineered a self-contained epidural
stimulation device that can be deployed in freely behaving rats to stimulate sensorimotor circuitry from multiple
surfaces of the spinal cord. Hence, we are well positioned to test critically important hypotheses on the role of
cervical stimulation in the restoration of upper limb function. We present exciting preliminary data demonstrating
that epidural stimulation of the cervical spinal cord improves forelimb function. The rationale for the proposed
research is that the site of epidural stimulation provides unique access to motor circuitry. We hypothesize that
ventral positioning of electrodes (VSS) will provide access to stimulate motor circuitry at the site of
lesion that are inaccessible from the more common dorsal approach (DSS). Further, we propose that
VSS will produce novel mechanisms of function plasticity that can amplify recovery when combined with
DSS. To test this hypothesis, we propose the following aims: Aim 1: Determine acute molecular and physiological
mechanisms of VSS when applied to subacute cervical spinal cord injury. Aim 2: Establish the functional impact
of site of stimulation and rehabilitative training on recovery from early chronic cervical spinal cord injury. Aim 3:
Establish the synergistic effects of combined VSS and DSS after cervical spinal cord injury. These studies will
explore an exciting new approach to promote neural recovery of the upper limb, an area of research that has
had limited investigation, but remains a primary concern for the patient. Our approach will rigorously establish
the physiological and functional effects of the site of stimulation on the molecular and physiological mechanisms
of upper limb plasticity.
摘要
人们对使用电刺激来促进感觉运动和运动功能的恢复越来越感兴趣
神经损伤后的自主神经功能。我们实验室和其他实验室之前的研究已经证明
刺激腰椎节段会激活中枢模式生成器,进而促进站立
还有走路。然而,尽管有大量的动物、临床前和临床数据检验了
腰椎刺激,将神经调节应用于上肢颈脊髓的研究非常有限。
在此,我们提出了在上肢神经调节领域存在的基本盲点,包括
在哪里进行解剖学上的刺激,如何给药,特别是作用机制。霍纳实验室已经
建立了一种临床相关的大鼠颈脊髓损伤模型,并设计了一种自给式硬膜外
一种可在行为自由的大鼠身上部署的刺激装置,以从多个角度刺激感觉运动回路
脊髓的表面。因此,我们处于有利地位,可以检验关于
颈椎刺激在恢复上肢功能中的作用。我们提供了令人兴奋的初步数据来演示
硬膜外刺激颈髓可以改善前肢功能。建议的理由是
研究表明,硬膜外刺激的部位提供了进入运动神经回路的独特通道。我们假设
电极的腹侧定位(VSS)将提供刺激运动回路的通路
更常见的背侧入路(DSS)无法触及的病变。此外,我们建议
VSS将产生新的功能可塑性机制,当与VSS结合时,可以放大恢复
DSS。为了验证这一假设,我们提出了以下目标:目标1:确定急性分子和生理
VSS治疗亚急性颈髓损伤的机制。目标2:确定功能影响
刺激部位及康复训练对早期慢性颈脊髓损伤康复的影响。目标3:
建立颈髓损伤后VSS和DSS联合应用的协同效应。这些研究将
探索一种令人兴奋的新方法来促进上肢的神经恢复,这是一个已经
调查有限,但仍是患者最关心的问题。我们的方法将严格确立
刺激部位对分子生理机制的生理和功能影响
上肢的可塑性。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Philip J Horner其他文献
Philip J Horner的其他文献
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{{ truncateString('Philip J Horner', 18)}}的其他基金
Training in Neural Control of organ Degeneration and Regeneration (NeuralCODR)
器官退化和再生的神经控制培训(NeuralCODR)
- 批准号:
10620833 - 财政年份:2022
- 资助金额:
$ 46.94万 - 项目类别:
Patricia Levy Zusman International Workshop on Neuroregeneration (Zusman Workshop)
Patricia Levy Zusman 神经再生国际研讨会(Zusman 研讨会)
- 批准号:
10607404 - 财政年份:2022
- 资助金额:
$ 46.94万 - 项目类别:
Training in Neural Control of organ Degeneration and Regeneration (NeuralCODR)
器官退化和再生的神经控制培训(NeuralCODR)
- 批准号:
10410250 - 财政年份:2022
- 资助金额:
$ 46.94万 - 项目类别:
A versatile reporter for visualization of myelin plasticity in the genetically modified rat
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10303241 - 财政年份:2021
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CNS Neuroregeneration strategies: Discovery and Implementation
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9332048 - 财政年份:2017
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Astrocyte-specific ligand discovery by phage display
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Metabolic requirements of adult neural stem cells
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8068094 - 财政年份:2011
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Metabolic requirements of adult neural stem cells
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Combined stem cell transplantation and targeted microstimulation to direct the fo
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