Exploring mechanisms underlying SCF+G-CSF-enhanced recovery in chronic TBI.
探索 SCF G-CSF 增强慢性 TBI 恢复的潜在机制。
基本信息
- 批准号:10220357
- 负责人:
- 金额:$ 40.52万
- 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:2021-04-01 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAffectBone MarrowBrainBrain InjuriesBrain imagingCancer PatientCaringCerebrumChronicChronic PhaseCognitionCountryCre-LoxPDataDemyelinationsDependenceDevelopmentEmotionalEvaluationEventFDA approvedFamilyFinancial HardshipFutureGenerationsGoalsGranulocyte Colony-Stimulating FactorGrowth FactorHealthHematopoietic Cell Growth FactorsIndividualInjuryIpsilateralLeadLearningLifeLong-Term CareLongevityMediatingMedicalMedical Care CostsMemoryModelingMolecularMolecular BiologyMolecular and Cellular BiologyMotorMusNatural regenerationNeuritesNeurodegenerative DisordersOligodendrogliaOperative Surgical ProceduresPathologyPharmacologyPhysical therapyPublic HealthRecoveryRecovery of FunctionRehabilitation therapyResearchResearch PersonnelRiskSensoryStem Cell FactorStrokeStructureSurvivorsTBI treatmentTechnologyTestingTherapeuticTraumatic Brain InjuryTraumatic Brain Injury recoveryTreatment FactorUnited StatesWorkbasebrain repaircare costschemotherapydisabilityeconomic costefficacy evaluationenhancing factorevidence baseexosomefunctional improvementfunctional outcomesimprovedmacrophagemonocyteneurobehavioralnoveloligodendrocyte progenitorpreclinical studyproductivity losspsychologicrecruitrelating to nervous systemremyelinationrepairedstem cell biologystem cell therapystem cellstwo-photonwhite matteryoung adult
项目摘要
SUMMARY/ABSTRACT
Traumatic brain injury (TBI) represents a public health crisis in the United States. TBI is a very common injury
in young adults and causes long-term disabilities in cognition, learning and memory, emotional control, and
sensory and motor function. A severe TBI can lead to lifelong physical and psychological problems and
increase the risk of developing neurodegenerative diseases. Severe TBI in young adults is a significant public
health problem and national burden because their lifelong disabilities, permanent productivity loss, and long-
term daily care dependence not only seriously affect the life of an individual and their family but also create a
heavy financial burden in the United States.
In the traditional view, TBI is an event that only needs acute management and a brief period of rehabilitation.
Today’s notion is that TBI is the onset of a chronic health condition that requires therapies for improving
recovery months and years after TBI. However, no such a treatment is available in the chronic phase. The
chronic phase exists in a long period from 3 or 6 months after TBI and throughout an individual’s life span. The
lack of treatment to improve severe TBI recovery in the chronic phase is a critical problem for the country.
Using a severe TBI model in young adult mice, we have demonstrated significant improvements in functional
recovery by a combination treatment of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-
CSF) (SCF+G-CSF) in the chronic phase. However, it remains unclear how SCF+G-CSF treatment in the
chronic phase of severe TBI improves functional recovery. The objective of this application is to determine the
underlying mechanisms of the SCF+G-CSF-enhanced recovery in chronic TBI. Based on preliminary studies,
we hypothesize that SCF+G-CSF-improved severe TBI recovery in the chronic phase is mediated by the
enhancement of cerebral remyelination and neurostructural regeneration. Using the approaches of molecular
and cellular biology, pharmacology, Cre-LoxP technology, 2-photon live brain imaging and neurobehavioral
evaluation, this hypothesis will be tested through two Specific Aims. Aim 1 will determine how SCF+G-CSF
treatment in the chronic phase of severe TBI enhances remyelination in cerebral white matter, and Aim 2 will
define how SCF+G-CSF treatment in the chronic phase of severe TBI enhances neural structure regeneration.
Searching for treatments to improve severe TBI recovery in the chronic phase is a highly-important-but-not-
investigated field and an urgent national demand to improve the health of young adults living with severe TBI. It
is expected that the accomplishment of the proposed mechanistic studies will significantly move the TBI
research field forward by identifying a unique pharmacological approach to repair a severe TBI-damaged brain
in the chronic phase.
摘要/文摘
项目成果
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{{ truncateString('LI-RU ZHAO', 18)}}的其他基金
Exploring mechanisms underlying SCF+G-CSF-enhanced recovery in chronic TBI.
探索 SCF G-CSF 增强慢性 TBI 恢复的潜在机制。
- 批准号:
10741338 - 财政年份:2023
- 资助金额:
$ 40.52万 - 项目类别:
Exploring Mechanisms Underlying SCF+G-CSF-Enhanced Recovery in ChronicTBI
探索 SCF G-CSF 增强慢性 TBI 恢复的机制
- 批准号:
10810929 - 财政年份:2021
- 资助金额:
$ 40.52万 - 项目类别:
Exploring mechanisms underlying SCF+G-CSF-enhanced recovery in chronicTBI.
探索 SCF G-CSF 增强慢性 TBI 恢复的机制。
- 批准号:
10376341 - 财政年份:2021
- 资助金额:
$ 40.52万 - 项目类别:
Revealing novel pathogenic and repairing mechanisms of CADASIL disease.
揭示 CADASIL 疾病的新致病和修复机制。
- 批准号:
10419211 - 财政年份:2021
- 资助金额:
$ 40.52万 - 项目类别:
Exploring Mechanisms Underlying SCF+G-CSF-Enhanced Recovery in ChronicTBI
探索 SCF G-CSF 增强慢性 TBI 恢复的机制
- 批准号:
10605216 - 财政年份:2021
- 资助金额:
$ 40.52万 - 项目类别:
Targeting the hematopoietic system: the role of hematopoietic growth factors in restricting A-beta accumulation in Alzheimers disease
靶向造血系统:造血生长因子在限制阿尔茨海默病中 A-β 积累中的作用
- 批准号:
9377021 - 财政年份:2016
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Targeting the hematopoietic system: the role of hematopoietic growth factors in restricting A-beta accumulation in Alzheimers disease
靶向造血系统:造血生长因子在限制阿尔茨海默病中 A-β 积累中的作用
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9357507 - 财政年份:2016
- 资助金额:
$ 40.52万 - 项目类别:
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