Optogenetics to improve hand function after spinal cord injury.
光遗传学改善脊髓损伤后的手部功能。
基本信息
- 批准号:10470835
- 负责人:
- 金额:$ 62.53万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-15 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAffectAnatomyAnimal ModelAnimalsAxonBloodBlood flowBrainBypassCervicalCervical spinal cord injuryCervical spinal cord structureChronicClinicalContusionsDataElectric StimulationElectrodesElectrophysiology (science)Exposure toFOS geneFiberForelimbFunctional disorderGenesGoalsHandHistologyImmunohistochemistryImplantImplantation procedureIn Situ HybridizationInjuryIon ChannelIschemiaLabelLightLightingMediatingMethodsModelingMovementNervous System TraumaNeuroanatomyNeuronsNeurostimulation procedures of spinal cord tissueOpsinOpticsParalysedParesisPersonsPolymersProteinsRandomizedRattusRecoveryRecovery of FunctionResearchRespiratory physiologyRodentSiteSpinalSpinal CordSpinal Cord ContusionsSpinal cord injuryStimulusSurfaceSynapsesTechnologyTestingTrainingUp-RegulationUpper ExtremityViralWorkarmarm functionaxon growthbasebiomaterial compatibilitycell typeepidural spaceexperimental studyflexibilityhand rehabilitationimplantationimprovedimproved functioninginjury recoveryinnovationmechanical propertiesneural circuitnoveloptogeneticsrecruitrelating to nervous systemresponsetreatment groupwaveguide
项目摘要
Project Summary/Abstract
Restoration of hand and arm function is the highest treatment priority for people with cervical spinal cord
injury. The goal of this research is to develop and test a novel method to improve recovery of hand and arm
function after spinal cord injury. We propose to use optogenetic stimulation of the cervical spinal cord to both
improve function and to uncover the mechanisms by which spinal cord stimulation leads to recovery.
Our preliminary data demonstrate both a rapid and near complete recovery of forelimb function when
animals receive optogenetic spinal cord stimulation following a clinically-realistic cervical spinal cord contusion
injury. Optogenetic light stimulation may provide benefits by both directly activating neural circuits and also by
increase blood flow to the injured spinal cord. Here we propose to compare the functional recovery resulting
from optogenetic and electrical spinal cord stimulation, as well as the combination of electrical and light
stimulation delivered to naïve animals that do not express optogenetic proteins.
Our experiments are enabled by a novel multifunctional electrode that permits both optical and electrical
stimulation to be delivered to the surface of the spinal cord in rodents. These flexible polymer electrodes will be
refined in Aim 1 to deliver chronic optogenetic and epidural electrical stimulation to the rat cervical spinal cord.
Thus all animals will be implanted with identical hardware prior to being randomized into treatment groups to
permit a direct comparison between optogenetic and electrical stimulation in Aim 2.
We will use our established rat model of spinal contusion injury where animals are trained to perform
precision forelimb reaching to accurately quantify recovery of function after injury. Our collaborative team has
developed a reliable method of viral transduction of optogenetic proteins such that light-sensitive ion channels
are expressed in neurons of the non-transgenic rat cervical spinal cord. Following 6-weeks of treatment with
optogenetic and epidural electrical stimulation, we will explore the mechanisms by which each treatment leads
to prolonged recovery of forelimb function in Aim 3. We will perform terminal electrophysiology and record the
responses evoked by both optical and electrical stimulation in the same animals.
Our preliminary data demonstrate an upregulation of axon growth following optogenetic stimulation. We will
use retrograde trans-synaptic tracing and histology to quantify new circuit formation bypassing the injury.
Labelled neurons will be co-localized with the neurons activated by optogenetic vs. epidural stimulation using
combined in-situ hybridization and immunohistochemistry to illuminate mechanisms of recovery.
In summary, we propose to uncover the mechanisms by which optogenetic spinal cord stimulation leads to
nearly complete recovery of forelimb function following spinal cord injury. Once understood, we expect these
mechanism to directly inspire treatments for a range of neurological traumas to the brain and spinal cord.
项目总结/摘要
恢复手和手臂功能是颈脊髓损伤患者的最高治疗优先事项
损伤本研究的目标是开发和测试一种改善手和手臂康复的新方法
脊髓损伤后的功能我们建议使用颈脊髓的光遗传学刺激,
改善功能并揭示脊髓刺激导致恢复的机制。
我们的初步数据表明,当
动物在临床上真实的颈脊髓挫伤后接受光遗传学脊髓刺激
损伤光遗传学光刺激可以通过直接激活神经回路以及还通过激活神经回路来提供益处。
增加受伤脊髓的血流量在这里,我们建议比较功能恢复结果
从光遗传学和电脊髓刺激,以及电和光的组合,
刺激递送至不表达光遗传学蛋白的幼稚动物。
我们的实验是由一种新型的多功能电极,允许光学和电学
刺激传递到啮齿动物的脊髓表面。这些柔性聚合物电极将被
在目的1中改进了将慢性光遗传学和硬膜外电刺激递送到大鼠颈脊髓。
因此,所有动物将在随机分配至治疗组之前植入相同的硬件,
允许直接比较Aim 2中的光遗传学和电刺激。
我们将使用我们建立的脊髓挫伤大鼠模型,动物在那里接受训练,
精确的前肢到达,以准确量化受伤后的功能恢复。我们的合作团队拥有
开发了一种可靠的病毒转导光遗传蛋白的方法,
在非转基因大鼠颈脊髓的神经元中表达。治疗6周后,
光遗传学和硬膜外电刺激,我们将探讨每种治疗导致的机制,
目标3中前肢功能的延长恢复。我们将进行终末电生理学检查并记录
在相同的动物中由光和电刺激引起的反应。
我们的初步数据表明,上调轴突生长后光遗传刺激。我们将
使用逆行跨突触追踪和组织学来量化绕过损伤的新回路形成。
标记的神经元将与通过光遗传学刺激与硬膜外刺激激活的神经元共定位,
结合原位杂交和免疫组织化学来阐明恢复的机制。
总之,我们建议揭示光遗传学脊髓刺激导致
脊髓损伤后前肢功能几乎完全恢复。一旦理解,我们期望这些
该机制直接激发了对大脑和脊髓的一系列神经创伤的治疗。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
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 }}
Polina O Anikeeva其他文献
Polina O Anikeeva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('Polina O Anikeeva', 18)}}的其他基金
Fusion of nanomagnetic and viral tools to interrogate brain-body circuits
融合纳米磁性和病毒工具来询问脑体回路
- 批准号:
10672302 - 财政年份:2021
- 资助金额:
$ 62.53万 - 项目类别:
Fusion of nanomagnetic and viral tools to interrogate brain-body circuits
融合纳米磁性和病毒工具来询问脑体回路
- 批准号:
10261671 - 财政年份:2021
- 资助金额:
$ 62.53万 - 项目类别:
Optogenetics to improve hand function after spinal cord injury.
光遗传学改善脊髓损伤后的手部功能。
- 批准号:
10252778 - 财政年份:2020
- 资助金额:
$ 62.53万 - 项目类别:
Wireless Magnetomechanical Neuromodulation of Targeted Circuits
目标电路的无线磁力神经调节
- 批准号:
9924842 - 财政年份:2020
- 资助金额:
$ 62.53万 - 项目类别:
Multi-Site Non-Invasive Magnetothermal Excitation and Inhibition of Deep Brain Structures
脑深部结构的多位点非侵入性磁热激发和抑制
- 批准号:
9357724 - 财政年份:2016
- 资助金额:
$ 62.53万 - 项目类别:
Multi-Site Non-Invasive Magnetothermal Excitation and Inhibition of Deep Brain Structures
脑深部结构的多位点非侵入性磁热激发和抑制
- 批准号:
9229172 - 财政年份:2016
- 资助金额:
$ 62.53万 - 项目类别:
Fiber Inspired Neural Probes for the Multifunctional Dynamic Brain Mapping
用于多功能动态脑图绘制的纤维启发神经探针
- 批准号:
8886012 - 财政年份:2015
- 资助金额:
$ 62.53万 - 项目类别:
Fiber Inspired Neural Probes for the Multifunctional Dynamic Brain Mapping
用于多功能动态脑图绘制的纤维启发神经探针
- 批准号:
9199380 - 财政年份:2015
- 资助金额:
$ 62.53万 - 项目类别:
Fiber Inspired Neural Probes for the Multifunctional Dynamic Brain Mapping
用于多功能动态脑图绘制的纤维启发神经探针
- 批准号:
9005888 - 财政年份:2015
- 资助金额:
$ 62.53万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 62.53万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 62.53万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 62.53万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 62.53万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 62.53万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 62.53万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 62.53万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 62.53万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 62.53万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 62.53万 - 项目类别:
Research Grant