KCC2 and Spinal Cord Injury
KCC2 和脊髓损伤
基本信息
- 批准号:10599160
- 负责人:
- 金额:$ 42.02万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-03-15 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:4-AminopyridineAgonistAnatomyAxonBilateralBrainCell membraneChronicContusionsDown-RegulationEsthesiaGrowthHindlimbHumanIGF1 geneImmunohistochemistryIn Situ HybridizationInjuryLesionLightLumbar spinal cord structureMediatingMembraneMessenger RNAModelingMotorMotor CortexMotor NeuronsMovementMusMuscleMuscular AtrophyNeuronsParalysedPathway interactionsPatientsPlayProteinsRattusRecovery of FunctionRehabilitation therapyRoleSpinalSpinal CordSpinal cord damageSpinal cord injuryTestingTimeTrainingVertebral columnclinically relevantdeprivationdesignexcitatory neuronfunctional restorationglial cell-line derived neurotrophic factorinhibitory neuroninsightnerve supplynovelnovel strategiesosteopontinoverexpressionrestorationtransmission process
项目摘要
Abstract/Project Summary
Most human spinal cord injuries (SCIs) are anatomically incomplete, with spared axons spanning the
damaged spinal segments. However, about a half of these patients have a total loss of muscle control and
sensation below the injury level. An important but under-studied question is why such spared connections
fail to mediate functional recovery in these cases. Recent advances in human studies show that epidural
stimulation combined with rehabilitative training allows some chronically paralyzed patients with SCI to
regain voluntary movement, highlights the feasibility of reactivating such dormant spinal circuitry. However,
the limited functional recovery only occurs when the stimulation is on. Thus, understanding why this spared
spinal circuitry is dysfunctional after SCI, and how it can best be reactivated, should provide key insights
into developing novel functional restoration strategies for SCI. In mice with staggered bilateral hemisections,
in which the lumbar spinal cord is deprived of all direct brain-derived innervation but dormant relay circuits
remain between the damaged segments, we discovered that systematic treatment with a KCC2 agonist, or
over-expression of KCC2, is able to restore stepping ability in these paralyzed mice. We showed that such
manipulations are able to correct over-inhibition within the spinal relay zone, allowing this detour circuit to
transmit the brain-derived commands to the hindlimb motor command center in the lumbar spinal cord,
leading to functional recovery. With these exciting preliminary results, this proposed study will address
several related questions: what is the mechanism underlying injury-induced KCC2 down-regulation in
injured spinal cord? Why the achieved functional recovery is partial and how to further enhance such
functional recovery? What are the effects of these circuit-modifying treatments in more clinically relevant
injury models, namely severe contusion models?
抽象/项目总结
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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ZHIGANG HE其他文献
ZHIGANG HE的其他文献
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{{ truncateString('ZHIGANG HE', 18)}}的其他基金
Mechanism and Optimization of CBD-mediated analgesic effects
CBD介导的镇痛作用机制及优化
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10288673 - 财政年份:2019
- 资助金额:
$ 42.02万 - 项目类别:
Mechanism and Optimization of CBD-mediated analgesic effects
CBD介导的镇痛作用机制及优化
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10662464 - 财政年份:2019
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$ 42.02万 - 项目类别:
Mechanism and Optimization of CBD-mediated analgesic effects
CBD介导的镇痛作用机制及优化
- 批准号:
10018669 - 财政年份:2019
- 资助金额:
$ 42.02万 - 项目类别:
Mechanism and Optimization of CBD-mediated analgesic effects
CBD介导的镇痛作用机制及优化
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10227071 - 财政年份:2019
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CRSIPR screening for novel regulators of retinal ganglion cell survival and axonal regeneration
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9920148 - 财政年份:2019
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Mechanism and optimization of CBD-mediated analgesic effects (Diversity Supplement)
CBD介导的镇痛作用的机制和优化(多样性补充)
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CRSIPR screening for novel regulators of retinal ganglion cell survival and axonal regeneration
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10402334 - 财政年份:2019
- 资助金额:
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