Combined Biomaterial and Neuromodulatory Approach to Promote Axonal Outgrowth and Connections After Cervical SCI
结合生物材料和神经调节方法促进宫颈 SCI 后轴突生长和连接
基本信息
- 批准号:10323048
- 负责人:
- 金额:$ 15.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-01-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAnimal ModelAnti-Inflammatory AgentsAxonBiocompatible MaterialsBrainCathodesCell SurvivalCervicalCervical spinal cord injuryChestChitosanCicatrixContusionsCorticospinal TractsDorsalElectric StimulationEngineeringEnvironmentExtracellular MatrixFRAP1 geneForelimbFormulationGrowthHumanHydrogelsInjuryInterneuronsInterruptionLeadLegal patentLesionMethodsModelingMotorMotor CortexMovementMuscleMuscle ContractionNeuronsNeuropilNeurostimulation procedures of spinal cord tissueParalysedPersonsPropertyPublishingRattusRecoveryRetinal Ganglion CellsSignal PathwaySignal TransductionSiteSpinalSpinal CordSpinal InjuriesSpinal cord injurySuspensionsSystemTissuesTranslatingaxon growthaxon regenerationaxonal sproutingbasefunctional restorationimplantationimprovedimproved functioninginjury and repairmotor controlmotor function improvementmotor function recoverymotor recoveryneuroregulationnovelnovel strategiespreventrelating to nervous systemrepair strategyrepairedresponseskillsspinal tractsynaptogenesistissue repairtransneuronal degeneration
项目摘要
Spinal cord injury (SCI) interrupts connections between the motor cortex (MCX) and spinal motor circuits. We
propose a novel approach to treat paralysis and weakness after spinal cord injury (SCI) by combining (1) dual MCX and
spinal cord stimulation to promote corticospinal tract (CST) axonal outgrowth and activity-dependent synapse formation,
and (2) implantation at the spinal injury site of a hydrogel biomaterial.
MCX epidural stimulation is a neuromodulatory approach that upregulates the mTOR and Jak/Stat signaling
pathways—essential for CST axon regeneration and CST injury-dependent sprouting—to promote CST axon sprouting,
synapse formation, and motor function after injury. The effects of MCX stimulation therapy is potentiated by cathodal
trans-spinal direct current stimulation (tsDCS), a non-invasive neuromodulatory approach that can be rostrocaudally-
targeted to activate the spinal cord.
However, the recovery that can be achieved by activity-based repair strategies is limited by the physical damage and
the cavity at the injury site. Our dual neuromodulatory strategy, alone, cannot achieve sufficient CST outgrowth and
circuit repair needed to restore significant function after a traumatic SCI. To achieve greater motor recovery after SCI, we
will combine neuromodulation with implantation of Chitosan engineered as a fragmented physical hydrogel suspension
(Chitosan-FPHS). This new and patented formulation remodels the injury site. Chitosan-FPHS helps abrogate physical
barriers at the lesion site and enhances axonal growth into and through the injury. Chitosan-FPHS therapy significantly
improves motor function after thoracic hemisection.
In this proposal, we use an adult rat C4 midline contusion model and combine published biomaterial implantation and
neuromodulation methods in a novel way to repair the motor system. In Aim 1, we will determine the efficacy of
Chitosan-FPHS hydrogel implantation combined with the dual neuromodulation therapy in promoting CST axonal
outgrowth and MCX evoked spinal cord and muscle responses. In Aim 2, we will determine the efficacy of Chitosan-
FPHS hydrogel implantation combined with dual neuromodulation therapy in promoting motor function after cervical
SCI.
Together, our combined neuromodulatory and biomaterial-based approach aims to induce persistent structural
plasticity after SCI. This approach could lead to recovery of substantial motor control in our animal model and could be
translated to improve function in people with SCI.
脊髓损伤(SCI)阻断了运动皮质(MCX)和脊髓运动回路之间的联系。我们
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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John H Martin其他文献
John H Martin的其他文献
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{{ truncateString('John H Martin', 18)}}的其他基金
Interaction of Motor Learning with Transcranial Direct Current - Efficacy and Mechanisms
运动学习与经颅直流电的相互作用 - 功效和机制
- 批准号:
10577313 - 财政年份:2022
- 资助金额:
$ 15.7万 - 项目类别:
Repairing maladaptive corticospinal tract development
修复适应不良的皮质脊髓束发育
- 批准号:
8654370 - 财政年份:2013
- 资助金额:
$ 15.7万 - 项目类别:
Repairing maladaptive corticospinal tract development
修复适应不良的皮质脊髓束发育
- 批准号:
8597664 - 财政年份:2013
- 资助金额:
$ 15.7万 - 项目类别:
Repairing maladaptive corticospinal tract development
修复适应不良的皮质脊髓束发育
- 批准号:
9256549 - 财政年份:2013
- 资助金额:
$ 15.7万 - 项目类别:
Repairing maladaptive corticospinal tract development
修复适应不良的皮质脊髓束发育
- 批准号:
8842211 - 财政年份:2013
- 资助金额:
$ 15.7万 - 项目类别:
Lesion and activity dependent corticospinal tract plasticity
病变和活动依赖性皮质脊髓束可塑性
- 批准号:
10413055 - 财政年份:2009
- 资助金额:
$ 15.7万 - 项目类别:
Diversity Supplement: Lesion and Activity Dependent Corticospinal Tract Plasticity
多样性补充:病变和活动依赖性皮质脊髓束可塑性
- 批准号:
10431593 - 财政年份:2009
- 资助金额:
$ 15.7万 - 项目类别:
Lesion and activity dependent corticospinal tract plasticity
病变和活动依赖性皮质脊髓束可塑性
- 批准号:
7730193 - 财政年份:2009
- 资助金额:
$ 15.7万 - 项目类别:
Lesion and activity dependent corticospinal tract plasticity
病变和活动依赖性皮质脊髓束可塑性
- 批准号:
10176602 - 财政年份:2009
- 资助金额:
$ 15.7万 - 项目类别:
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