Functional three dimensional brain-like tissues to study mechanisms of traumatic brain injury
功能性三维类脑组织用于研究创伤性脑损伤的机制
基本信息
- 批准号:9266832
- 负责人:
- 金额:$ 35.55万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-07-01 至 2020-04-30
- 项目状态:已结题
- 来源:
- 关键词:AccelerationAcuteAddressAdultAdverse effectsAnimalsAnxietyAstrocytesBiochemicalBlood - brain barrier anatomyBrainBrain ConcussionBrain InjuriesCandidate Disease GeneCellsCerebral VentriclesCerebrospinal FluidChildChronicClinical TrialsClosed head injuriesCognitiveCognitive deficitsContusionsCortical ContusionsCoupledCouplingCraniocerebral TraumaDataDecelerationDimensionsDropsElectrophysiology (science)EpidemicFRAP1 geneFunctional disorderGene DeletionGene-ModifiedGeneticGoalsHistologyHourHumanImpaired cognitionIn VitroIndividualInjectableInjuryInterleukin-1 ReceptorsInterventionKnowledgeLongevityMechanicsMethodsMicrogliaModelingMolecularMotor ActivityMusNeurologicNeuronsOutcomeOutcome AssessmentPathway interactionsPerfusionPhysiologicalPreventionPreventive measureProcessRNARehabilitation therapyReportingRiskRodentRoleRouteStructureSystemTNF geneThinkingTimeTissue ModelTissuesTransplantationTraumaTraumatic Brain InjuryUnited StatesWeightbrain repairbrain tissuecell typecontrolled cortical impactcosthealinghuman tissueimprovedin vivoin vivo Modelinjuredinjury and repairinsightmetabolomicsmouse modelnovelnovel strategiespreclinical studypublic health relevancerepairedresponseresponse to injurythree dimensional cell culturetranscriptometranscriptomics
项目摘要
DESCRIPTION (provided by applicant): There is a significant need for new insights into mechanisms of brain damage due to trauma. Damage due to different types of head trauma, from focal contusions to concussions, requires new thinking about methods and outcomes to provide windows for treatment to ameliorate this major risk to children and adults, as well new preventative measures. To address this major and growing need we plan to utilize novel 3D brain-like tissues in vitro, coupled with animal studies, to correlate markers and mechanisms of injury and response. Our hypothesis is that 3D mouse and human brain-like tissues with structural and functional features mimicking in vivo conditions will provide physiologically-relevant readouts for the study of brain function and responses to mechanical damage to study mechanisms involved in traumatic brain injury and repair. Such correlations will provide new and important insight into pathways activated by injury, how the type of injury effects different pathways, how the brain heals in response to these different pathways, and to help identify new leads for intervention and treatments. The coupling of in vitro 3D tissues (rodent and human) with in vivo rodent studies, impacted by different types of damage (e.g., inertial and weight drop), will provide a comprehensive assessment of outcomes not previously pursued, while also improving translational relevance. The availability of tissue models that sustain structure and function for months allows for both acute and chronic assessments of outcomes (genetic, biochemical, metabolomics, electrophysiological). These readouts will offer unprecedented insight and interpretation of cause and effect to these types of injuries. Our initial insight into
mechanisms, such as involving Akt and mTOR activation, will provide suitable starting points for further study, while transcriptomics will allow for the identification of new leads. Ultimately, comparing transcriptome responses between the in vitro and in vivo models, along with the other readouts planned, and doing so in both acute and chronic temporal responses in vitro and in vivo, should provide unprecedented new insight into damage effects and modes for intervention. All of the plans are supported with extensive preliminary data.
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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DAVID L. KAPLAN的其他文献
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{{ truncateString('DAVID L. KAPLAN', 18)}}的其他基金
2023 Silk Proteins and the Transition to Biotechnologies Gordon Research Conference
2023 年丝蛋白和向生物技术的过渡戈登研究会议
- 批准号:
10681751 - 财政年份:2023
- 资助金额:
$ 35.55万 - 项目类别:
Functional three dimensional brain-like tissues to study mechanisms of traumatic brain injury
功能性三维类脑组织用于研究创伤性脑损伤的机制
- 批准号:
8942566 - 财政年份:2015
- 资助金额:
$ 35.55万 - 项目类别:
Multifunctional Tropoelastin-Silk Biomaterial Systems
多功能原弹性蛋白-丝生物材料系统
- 批准号:
8518096 - 财政年份:2012
- 资助金额:
$ 35.55万 - 项目类别:
In vitro bioreactor sys for platelet formation
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8723656 - 财政年份:2012
- 资助金额:
$ 35.55万 - 项目类别:
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