Delayed white matter loss in concussive head injuries and its treatment
颅脑震荡迟发性脑白质丢失及其治疗
基本信息
- 批准号:10354469
- 负责人:
- 金额:$ 25.53万
- 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:2021-12-01 至 2022-11-30
- 项目状态:已结题
- 来源:
- 关键词:Action PotentialsAcuteAnimal ModelAnimalsAnisotropyAnxietyAxonBehaviorBehavioralBiological MarkersBrainBrain ConcussionBrain InjuriesBrain imagingChronicClinicalClinical TrialsClinical/RadiologicClosed head injuriesCollaborationsComplementCorpus CallosumCorrelation StudiesCraniocerebral TraumaCyclic ADP-RiboseDataDiffusion Magnetic Resonance ImagingEvolutionFiberFunctional Magnetic Resonance ImagingFutureGliosisGrowth Associated Protein 43HistologicImageIndividualInjuryInternal CapsuleInterventionIntranasal AdministrationLIF geneLeadMagnetic Resonance ImagingMethodsMissionModalityModelingMonitorMultimodal ImagingMusMyelinNatural regenerationNerve DegenerationNervous System PhysiologyNeuritesNeurologicNeurologic DeficitNeurological outcomeNeuronal InjuryNeuronsOutcome StudyPatientsPhasePopulationProceduresProcessPrognosisProtocols documentationPublic HealthRadiology SpecialtyRattusRecoveryResearchResolutionResourcesRestSiteStudy modelsTestingTherapeuticTimeTissuesTraumatic Brain InjuryTreatment outcomeUnited States National Institutes of HealthUniversitiesVeteransWateraxon injuryaxon regenerationaxonal degenerationbaseblood oxygen level dependentclinically relevantcohortcytokineexperimental studyfunctional declineimaging biomarkerimaging studyimprovedin vivo imagingindexingmild traumatic brain injurymultimodalitymyelinationneocorticalneonatal hypoxic-ischemic brain injuryneurophysiologyneurovascularneurovascular couplingnovelpre-clinicalpreservationpreventregeneration functionregenerativerelating to nervous systemresponsetranslation to humanswhite matterwhite matter injury
项目摘要
Abstract.
Half of all traumatic brain injuries cause changes in white matter integrity. Whereas progress is being made in
understanding the mechanisms that lead to acute axonal injury, there is an unmet need for therapeutics to
prevent delayed neuronal injury and restore neurological function. We recently demonstrated that the acute
intranasal (IN) administration of the cytokine Leukemia Inhibitory factor (LIF) reduced gliosis, preserved
corpus callosal myelination, preserved neocortical volumes and improved sensorimotor behavior in a
neonatal hypoxic-ischemic brain injury. Here, in a mouse closed head injury (CHI) TBI model, we show that
delayed IN LIF Rx prevents sensorimotor functional decline and reduces anxiety when IN LIF Rx is initiated at
6 wks of recovery. Therefore, our overall hypothesis is that intranasal LIF Rx can decrease neurological
deficits after TBI by preventing delayed white matter injury and nurturing axonal regeneration by inhibiting
SARM1 activation. Unequivocally demonstrating that an intervention is slowing a degenerative process and
nurturing regeneration requires monitoring over time to show that it prevents the evolution of tissue damage
and stimulates regeneration. Therefore, we propose to utilize high resolution multiple modality live animal
magnetic resonance imaging to determine the structural and functional changes in response to IN LIF Rx. We
will complement the in vivo imaging with ex-vivo diffusion tensor imaging studies and will correlate the
findings with histological and neurological functional analyses. These studies will pave the way for future
clinical trials where similar radiological markers can be assessed to prevent delayed white matter injury.
1
抽象的。
所有创伤性脑损伤中有一半会导致白质完整性发生变化。尽管正在取得进展
了解导致急性轴突损伤的机制后,对治疗方法的需求尚未得到满足
预防迟发性神经元损伤,恢复神经功能。我们最近证明,急性
鼻内 (IN) 施用细胞因子白血病抑制因子 (LIF) 可减少神经胶质增生,并保留
胼胝体髓鞘形成,保留新皮质体积并改善感觉运动行为
新生儿缺氧缺血性脑损伤。在这里,在小鼠闭合性头部损伤 (CHI) TBI 模型中,我们表明
当 IN LIF Rx 开始时,延迟 IN LIF Rx 可防止感觉运动功能下降并减少焦虑。
6周恢复。因此,我们的总体假设是鼻内 LIF Rx 可以降低神经功能
通过预防迟发性白质损伤和通过抑制来促进轴突再生来治疗 TBI 后的缺陷
SARM1 激活。明确证明干预措施正在减缓退化过程并且
培育再生需要随着时间的推移进行监测,以表明它可以防止组织损伤的演变
并刺激再生。因此,我们建议利用高分辨率多模态活体动物
磁共振成像以确定 IN LIF Rx 响应的结构和功能变化。我们
将补充体内成像与离体扩散张量成像研究,并将关联
组织学和神经功能分析的结果。这些研究将为未来铺平道路
可以评估类似放射标志物以预防迟发性白质损伤的临床试验。
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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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Dewan Syed Fahmeed Hyder其他文献
Dewan Syed Fahmeed Hyder的其他文献
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Delayed white matter loss in concussive head injuries and its treatment
颅脑震荡迟发性脑白质丢失及其治疗
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