Neuroprotective growth factors in traumatic brain injury
创伤性脑损伤中的神经保护性生长因子
基本信息
- 批准号:7544457
- 负责人:
- 金额:$ 34.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-12-01 至 2011-12-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdverse effectsAnimal BehaviorAreaBehavioralBilateralBrainBrain InjuriesBrain-Derived Neurotrophic FactorCandidate Disease GeneCell DeathCellsCognitiveCraniocerebral TraumaCritical PathwaysDataDevelopmentDoseExperimental Animal ModelGenesGrantGrowth FactorHippocampus (Brain)HumanIn VitroInfusion proceduresInjuryLearningMediatingMemoryMemory LossMemory impairmentMolecularMolecular AnalysisNeuronsOutcomePathway interactionsPatientsRelative (related person)Research PersonnelRetrograde amnesiaSignal TransductionSliceSurvivorsTestingTraumatic Brain InjuryUnited StatesUp-Regulationbehavior testcell injurycomparative efficacydisabilityexperiencehippocampal pyramidal neuronimprovedimproved functioningin vivoinsightneuron lossneuroprotectionneurotrophic factorneurotrophin 4oxidative damageprogramsreceptorresearch studytherapeutic development
项目摘要
In the United States, 1.4 million people each year suffer a traumatic brain injury. Of those who survive,
80-90,000 people per year experience long-term disabilities, often including retrograde amnesia and deficits
in learning and memory due to hippocampal neuronal cell loss. Bilateral loss of hippocampal neurons has
been observed in 85% of fatal human head injury cases. Within the hippocampus, pyramidal neurons are
particularly vulnerable to brain injury in humans as well as experimental animal models of TBI. Although the
cognitive problems are among the most long-lasting and debilitating outcomes in patients, no
neuroprotective therapy is available for this type of damage in human patients. Therefore, the need for the
development of therapeutic strategies aiming at protecting these cells is critical.
In the previous grant cycle, we identified a mammalian neurotrophin (NT4/5) that is neuroprotective for
pyramidal neurons. A related neurotrophin, brain-derived neurotrophic factor (BDNF) was ineffective. The
purpose of this proposal is to evaluate in detail the efficacy and mechanism of NT4/5-mediated hippocampal
neuroprotection. Our proposed experiments will determine the functional benefit of this new theraputic
molecule as well as the limitations associated with its use. Our Central Hypothesis is: NT4/5 rescue of
CAS pyramidal neurons after TBI improves hippocampal function via upregulation of a specific set of
neuroprotective genes. We will investigate this hypothesis by: (1) Determining whether NT4/5 treatment
improves hippocampal function after experimental traumatic brain injury; (2) Determining the mechanism of
NT4/5-mediated neuroprotection by examining 11 candidate genes upregulated by NT4/5 but not by BDNF;
and (3) Determining the critical parameters for NT4/5 rescue of hippocampal neurons.
We will use multiple levels of analysis (molecular, cellular, circuit and behavioral) to gain a detailed
understanding of the mechanism of NT4/5 neuroprotection. These findings will provide insight for developing
more specific therapies to ameliorate memory loss in TBI patients.
在美国,每年有140万人遭受脑外伤。幸存者中
每年有80- 90,000人经历长期残疾,通常包括逆行性遗忘和缺陷
海马神经元细胞的缺失导致学习和记忆能力下降。双侧海马神经元缺失
在85%的致命性人类头部损伤病例中观察到。在海马体中,锥体神经元
在人类以及TBI的实验动物模型中特别容易受到脑损伤。虽然
认知问题是患者最持久和最衰弱的结果之一,不是吗?
神经保护疗法可用于人类患者的这种类型的损伤。因此,需要
开发旨在保护这些细胞的治疗策略是至关重要的。
在上一个资助周期中,我们发现了一种哺乳动物神经营养因子(NT 4/5),
锥体神经元一种相关的神经营养因子,脑源性神经营养因子(BDNF)无效。的
本研究旨在详细评价NT 4/5介导的海马神经元凋亡的有效性和机制。
神经保护我们提出的实验将确定这种新疗法的功能效益。
分子以及与其使用相关的限制。我们的中心假设是:NT 4/5拯救
TBI后CAS锥体神经元通过上调一组特定的
神经保护基因我们将通过以下方式研究这一假设:(1)确定NT 4/5治疗是否
改善实验性创伤性脑损伤后海马功能;(2)确定
通过检查11个被NT 4/5上调但不被BDNF上调的候选基因来研究NT 4/5介导的神经保护作用;
(3)确定NT 4/5拯救海马神经元的关键参数。
我们将使用多个层次的分析(分子,细胞,电路和行为),以获得详细的
了解NT 4/5神经保护的机制。这些发现将为开发
更具体的治疗,以改善创伤性脑损伤患者的记忆丧失。
项目成果
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DEBORAH J WATSON其他文献
DEBORAH J WATSON的其他文献
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{{ truncateString('DEBORAH J WATSON', 18)}}的其他基金
Neuroprotective growth factors in traumatic brain injury
创伤性脑损伤中的神经保护性生长因子
- 批准号:
7997165 - 财政年份:2000
- 资助金额:
$ 34.57万 - 项目类别:
NEUROPROTECTIVE GROWTH FACTORS IN TRAUMATIC BRAIN INJURY
创伤性脑损伤中的神经保护生长因子
- 批准号:
6819711 - 财政年份:2000
- 资助金额:
$ 34.57万 - 项目类别:
Neuroprotective growth factors in traumatic brain injury
创伤性脑损伤中的神经保护性生长因子
- 批准号:
7746345 - 财政年份:2000
- 资助金额:
$ 34.57万 - 项目类别:
Neuroprotective growth factors in traumatic brain injury
创伤性脑损伤中的神经保护性生长因子
- 批准号:
7341671 - 财政年份:2000
- 资助金额:
$ 34.57万 - 项目类别:
LENTIVIRAL VECTOR GENE TRANSFER TO THE CNS IN MPS VII
MPS VII 中慢病毒载体基因转移至中枢神经系统
- 批准号:
6294618 - 财政年份:2000
- 资助金额:
$ 34.57万 - 项目类别:
Neuroprotective growth factors in traumatic brain injury
创伤性脑损伤中的神经保护性生长因子
- 批准号:
7197169 - 财政年份:2000
- 资助金额:
$ 34.57万 - 项目类别:
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