Senior Research Career Scientist
高级研究职业科学家
基本信息
- 批准号:10749218
- 负责人:
- 金额:--
- 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:2019-01-01 至 2030-12-31
- 项目状态:未结题
- 来源:
- 关键词:Activities of Daily LivingAffectAmericanAmputeesAmyotrophic Lateral SclerosisAnimal ModelAnti-Inflammatory AgentsAntioxidantsAreaAttenuatedBasic ScienceBathingBehaviorBeliefBiocompatible MaterialsBiologicalBloodBrainCaregiversCellsCellular immunotherapyCentral Nervous SystemCervicalCervical spinal cord injuryChemistryChronicClinicalComputersCorrosivesDedicationsDeep Brain StimulationDetectionDevicesDisabled PersonsDiseaseElectrodesEngineeringEnzymesFailureFecesGenesGeometryGoalsGovernmentHealthcareImmunityImplantIndividualInfiltrationInflammatoryInflammatory InfiltrateInflammatory ResponseInjuryInnate Immune SystemInstitutionInvestigationJournalsLaboratoriesLife ExpectancyLimb ProsthesisLiquid substanceLiteratureLongevityLower ExtremityManuscriptsMechanicsMediatingMethodsMicroelectrodesMilitary PersonnelMissionModelingModulusMolecularMotionMovementMuscleNamesNanotechnologyNatural ImmunityNatureNerve DegenerationNeuronsNeurosciencesOutcomeOxidative StressParalysedPathologicPathway interactionsPatientsPeer ReviewPerformancePersonsPharmaceutical PreparationsPolymersPrivatizationProcessProteinsPublishingQuadriplegiaQuality of lifeRecoveryRehabilitation therapyReportingResearchResearch PersonnelResolutionRibosomal RNARoboticsRoleScienceScientistSeizuresSelf-Help DevicesSeminalServicesShunt DeviceSignal TransductionSpecificitySpinal cord injurySpinal cord injury patientsSterilityStreamStrokeSystemTechnologyTherapeuticThinkingTimeTissuesTranslatingUpper ExtremityVentricularVeteransWorkarmbiomacromoleculeblood-brain barrier crossingbrain computer interfacebrain healthbrain machine interfacebrain tissuecareerclinical applicationcommunication devicedisabilityexperiencefallsfeedinggene therapygut microbiomeimplantable deviceimplantationimprovedindexinginjuredinterestlimb lossmaterials sciencemechanical devicemetallicitymicrobiomemimeticsmultidisciplinarynervous system disorderneuralneuroinflammationneuroprotectionneurotransmissionpre-clinicalresponsespatiotemporal
项目摘要
Overall goals: My laboratory strives to understand and facilitate the neuroinflammatory response to all implanted
devices within the central nervous system. Such devices range from ventricular shunts to various types of
stimulating and recording electrodes. However, most of my efforts have been on intracortical microelectrodes
due to their significance in research to understand the brain and the role in rehabilitative applications of Brain
Computer Interfacing, which is of particular interest to the VA. By understanding mechanism of failure, we can
pursue both materials-based and therapeutic-based methods to mitigate the inflammatory-mediated failure.
1) Role of tissue/device mechanical mismatch in microelectrode failure. We developed biologically inspired
materials for intracortical microelectrodes to independently examine and manipulate device modulus, geometry,
and drug-eluting capabilities. We have demonstrated that mechanically dynamic intracortical microelectrodes
are stiff enough to be inserted into the brain, become compliant to reduce micro-motion and inhibit late-stage
neuroinflammatory responses, can be fabricated into functional intracortical microelectrodes, and can be utilized
to deliver anti-inflammatory therapeutics from the device substrate or in combination with microfluid devices.
2) Role of oxidative stress in microelectrode failure. Oxidative pathways have been implicated in both
neurodegeneration and corrosive damage to both the metallic and insulating materials of current intracortical
microelectrode technologies. Thus, approaches to mitigate or attenuate the deleterious effects of oxidative
inflammatory products are of significant importance. We have demonstrated that several antioxidants can be
delivered systemically or locally to temporally mitigate neuronal damage and loss, and that bioactive coatings
with mimetic anti-oxidative enzymes can prolong neuroprotection and improve recording performance.
3) Role of specific immunity pathways in microelectrode failure. Pathological assessment of the
neuroinflammatory response to intracortical microelectrodes has been limited to a dozen or so known
neuroinflammatory proteins. We are using spatially resolved omics to developed one of the most comprehensive
analyses to date the microelectrode/tissue interface. By identifying genes and proteins of interest, we can then
explore hypotheses about specific innate immune systems or develop gene therapies for immune cell silencing.
4) Role of gut microbiome in microelectrode failure. Microbiome may play a role in modulating
neuroinflammation. Constituents of the gut microbiome can directly infiltrate the brain causing a local
inflammatory response, or act indirectly via metabolites or inflammatory factors that enter the blood stream and
cross the blood brain barrier. We utilized 16S rRNA analysis to show that the composition of gut-resident
microbiome in feces and brain tissue changes following microelectrode implantation and can be modulated
through treatment to impact the quality of chronic intracortical recordings. We seek to translate these findings
from preclinical to clinical therapies to improve microelectrode performance.
总体目标:我的实验室致力于了解和促进所有植入的神经炎症反应。
中枢神经系统内的装置。这种装置的范围从心室分流器到各种类型的分流器。
刺激和记录电极。然而,我的大部分努力都是在皮质内微电极上,
由于它们在研究中的重要性,以了解大脑和大脑的康复应用中的作用,
计算机接口,这是退伍军人管理局特别感兴趣的。通过了解失败的机制,我们可以
寻求基于材料和基于治疗的方法来减轻炎症介导的失败。
1)组织/器械机械不匹配在微电极失效中的作用。我们从生物学的角度
用于皮质内微电极的材料,以独立地检查和操纵装置的模量,几何形状,
和药物洗脱能力。我们已经证明,机械动态皮质内微电极
足够坚硬以插入大脑,变得顺应以减少微运动并抑制晚期
神经炎症反应,可以制成功能性皮质内微电极,并可以利用
以从装置基底或与微流体装置组合递送抗炎治疗剂。
2)氧化应激在微电极失效中的作用。氧化途径与这两种疾病都有关系。
神经变性和腐蚀性损伤的金属和绝缘材料的电流皮质内
微电极技术因此,减轻或减弱氧化应激的有害影响的方法是可行的。
炎性产物是非常重要的。我们已经证明,几种抗氧化剂可以
全身或局部递送以暂时减轻神经元损伤和损失,
与模拟抗氧化酶一起使用可以延长神经保护并改善记录性能。
3)特异性免疫途径在微电极失效中的作用。病理学评估
对皮质内微电极的神经炎症反应仅限于十几种已知的
神经炎性蛋白我们正在使用空间分辨组学来开发一个最全面的
分析微电极/组织界面的日期。通过识别感兴趣的基因和蛋白质,我们可以
探索关于特定先天免疫系统的假说或开发免疫细胞沉默的基因疗法。
4)肠道微生物组在微电极失效中的作用。微生物组可能在调节
神经炎症肠道微生物组的成分可以直接渗入大脑,
炎症反应,或通过进入血流的代谢物或炎症因子间接起作用,
穿过血脑屏障我们利用16 S rRNA分析表明,肠道居民的组成,
微电极植入后粪便和脑组织中的微生物组发生变化,
通过治疗来影响慢性皮质内记录的质量。我们试图将这些发现
从临床前到临床治疗,以改善微电极性能。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Mechanically Adaptive Implants Fabricated with poly(2-hydroxy-ethyl methacrylate-) based negative photoresists
使用聚(甲基丙烯酸 2-羟乙酯)基负光刻胶制造的机械自适应植入物
- DOI:10.1039/d0tb00980f
- 发表时间:2020
- 期刊:
- 影响因子:0
- 作者:Monney, B.
- 通讯作者:Monney, B.
Neuron-like neural probes.
类似神经元的神经探针。
- DOI:10.1038/s41563-019-0312-9
- 发表时间:2019
- 期刊:
- 影响因子:41.2
- 作者:Capadona,JeffreyR;Shoffstall,AndrewJ;Pancrazio,JosephJ
- 通讯作者:Pancrazio,JosephJ
Tools for Surface Treatment of Silicon Planar Intracortical Microelectrodes.
用于硅平面皮质内微电极表面处理的工具。
- DOI:10.3791/63500
- 发表时间:2022
- 期刊:
- 影响因子:0
- 作者:Krebs,OliviaK;Mittal,Gaurav;Ramani,Shreya;Zhang,Jichu;Shoffstall,AndrewJ;Cogan,StuartF;Pancrazio,JosephJ;Capadona,JeffreyR
- 通讯作者:Capadona,JeffreyR
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Jeffrey R Capadona其他文献
Jeffrey R Capadona的其他文献
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{{ truncateString('Jeffrey R Capadona', 18)}}的其他基金
Optimizing Delivery of a Known Therapeutic Agent, Dexamethasone, to Improve Microelectrode Recording Performance
优化已知治疗剂地塞米松的输送,以提高微电极记录性能
- 批准号:
10418649 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Optimizing Delivery of a Known Therapeutic Agent, Dexamethasone, to Improve Microelectrode Recording Performance
优化已知治疗剂地塞米松的输送,以提高微电极记录性能
- 批准号:
10642761 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Optimizing Delivery of a Known Therapeutic Agent, Dexamethasone, to Improve Microelectrode Recording Performance
优化已知治疗剂地塞米松的输送,以提高微电极记录性能
- 批准号:
10217285 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Characterizing and Mitigating the Role of Oxidative Damage in Microelectrode Failure
表征和减轻氧化损伤在微电极失效中的作用
- 批准号:
10599364 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Hybrid Drug-Eluting Microfluidic Neural Probe for Chronic Drug Infusion
用于慢性药物输注的混合药物洗脱微流控神经探针
- 批准号:
10356848 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Characterizing and mitigating the role of oxidative damage in microelectrode failure
表征和减轻氧化损伤在微电极故障中的作用
- 批准号:
10561933 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Hybrid Drug-Eluting Microfluidic Neural Probe for Chronic Drug Infusion
用于慢性药物输注的混合药物洗脱微流控神经探针
- 批准号:
10840055 - 财政年份:2019
- 资助金额:
-- - 项目类别:
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