A Mouse Model for Emotional Disorder Caused by Mild Traumatic Brain Injury
轻度创伤性脑损伤引起的情绪障碍小鼠模型
基本信息
- 批准号:8637562
- 负责人:
- 金额:$ 18.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-09-01 至 2015-08-31
- 项目状态:已结题
- 来源:
- 关键词:A MouseAccelerationAffectAge-YearsAirAir PressureAnimal ModelAnimalsAntigensAnxietyAreaAutoantibodiesAxonBehavioralBiological MarkersBlast CellBlood - brain barrier anatomyBrainBrain InjuriesBrain PathologyBrain regionC57BL/6 MouseCellsCephalicCerebrumChronicChronic DiseaseClosed head injuriesCognition DisordersCognitiveCognitive deficitsCorticosteroneDecelerationDefectDeteriorationDevelopmentDiffuse Axonal InjuryEmotionalEmotional DisturbanceEmotional disorderEventFrightFutureGoalsHeadHead MovementsHippocampus (Brain)HumanImpaired cognitionInjuryLeadLeftLifeLong-Term EffectsLungMediatingMemoryMemory LossMental DepressionMental HealthMild ConcussionsMilitary PersonnelModelingMolecularMotionMusNatureNeurobiologyNeurocognitiveNeurodegenerative DisordersNeuronsOutcomePathologyPlasmaProcessSerologicalSerumShockSimulateSportsStressStretchingSymptomsSystemTimeTraumatic Brain InjuryVascular Systembasebehavior testbrain tissuecombatcraniumdisabilityeffective therapyhyperphosphorylated tauinjuredinsightintercellular communicationinterestmalemouse modelneurogeneticsprematurepreventprogressive neurodegenerationprotein TDP-43public health relevancerelating to nervous systemstemtherapy developmenttime intervalvehicular accident
项目摘要
DESCRIPTION (provided by applicant): The cognitive and emotional disability that commonly results from mild traumatic brain injury (TBI) is a major public mental health problem. Only limited insight is available on how mild TBI alters brain to cause lasting cognitive and emotional symptoms, or how to effectively treat these symptoms. Mild TBI is an extremely common occurrence during military combat, sports, recreational activities, and vehicular accidents. Mild TBI involves closed-head injury from a primary blast shock wave, or head acceleration - deceleration during a collision. The resulting brain injury appears to stem from the rapid brain tissue deformation that results from the shock wave transmitted through brain by the blast, or from the brain compression - expansion during rapid head acceleration - deceleration. The rapidly alternating compression and stretching lead to neuronal alterations that are yet poorly characterized, and unknown secondary degenerative events that can cause lasting and, in the case of chronic traumatic encephalopathy (CTE), even intensifying symptoms. Although TBI has been modeled in animals using a variety of approaches, anxiety, depression, and memory loss caused by mild TBI have typically been characterized only over the short term (1 day - 2 weeks) and rarely over the long term (> 1 month). Accordingly, the molecular and cellular events by which a concussive event impairs cells and axons within specific brain regions to cause persistent symptoms or as a delayed effect are ill-defined. We have developed a mouse model of closed-head primary blast mild TBI using a controlled air pressure wave delivered to a small mid-cranial area. This model simulates the temporal and physical dynamics of the forces causing shock wave-mediated mild TBI. We have found that we can create hyper-anxiety and depression, and diffuse axonal injury, in 3-month old male C57BL/6 mice during the first month after 50-60 psi blast with this system. Our model thus recapitulates the insult and at least the short- term outcome commonly associated with mild concussions in humans. We propose to use our blast model of mild TBI to characterize anxiety, fear, depression and memory loss in male C57BL/6 mice over the 9-month period following single or multiple blasts. We will conduct histological assessments to relate behavioral deficits to pathology in specific brain regions, and serological assessments of biomarkers that are predictive and perhaps causally related (for example, autoantibodies against neural antigens) to the process causing secondary brain damage. Our studies will establish the time course over which cognitive and emotional abnormalities develop, wane, or worsen following single or repeat mild TBI. Our multiple blast studies will develop a mouse model for the progressive multi-concussive disorder CTE. The overall findings will provide parameters for reliably producing mild TBI that yields neurocognitive
and emotional disorder, to facilitate future studies of the neurobiological and neurogenetic basis of the emotional and cognitive deficits of mild TBI, and for the development of effective treatments.
描述(由申请人提供):认知和情感障碍,通常导致轻度创伤性脑损伤(TBI)是一个主要的公共心理健康问题。关于轻度TBI如何改变大脑以引起持久的认知和情绪症状,或者如何有效地治疗这些症状,只有有限的见解。轻度TBI在军事战斗,体育,娱乐活动和交通事故中非常常见。轻度TBI涉及来自主要爆炸冲击波的闭合性头部损伤,或碰撞期间的头部加速-减速。由此产生的脑损伤似乎源于爆炸通过大脑传递的冲击波导致的快速脑组织变形,或者源于头部快速加速-减速期间的大脑压缩-膨胀。快速交替的压缩和拉伸导致神经元改变,但特征不明显,以及未知的继发性退行性事件,这些事件可能导致持久的症状,在慢性创伤性脑病(CTE)的情况下,甚至会加剧症状。 尽管已经使用各种方法在动物中对TBI进行了建模,但是由轻度TBI引起的焦虑、抑郁和记忆丧失通常仅在短期内(1天-2周)表征,并且很少在长期内(> 1个月)表征。因此,脑震荡事件损害特定脑区域内的细胞和轴突以引起持续症状或作为延迟效应的分子和细胞事件是不明确的。我们已经开发了一个小鼠模型的封闭头原发爆炸轻度TBI使用受控的空气压力波传递到一个小的中颅区域。该模型模拟了引起冲击波介导的轻度TBI的力的时间和物理动力学。我们已经发现,在用该系统进行50-60 psi冲击后的第一个月期间,我们可以在3个月大的雄性C57 BL/6小鼠中产生过度焦虑和抑郁以及弥漫性轴突损伤。因此,我们的模型概括了人类轻度脑震荡的侮辱和至少短期结果。 我们建议使用我们的爆炸模型轻度TBI的特征焦虑,恐惧,抑郁和记忆丧失的雄性C57 BL/6小鼠在9个月的时间后,单次或多次爆炸。我们将进行组织学评估,将行为缺陷与特定脑区的病理学联系起来,并对生物标志物进行血清学评估,这些生物标志物具有预测性,可能与引起继发性脑损伤的过程有因果关系(例如,针对神经抗原的自身抗体)。我们的研究将建立认知和情绪异常在单次或重复轻度TBI后发展、减弱或恶化的时间过程。我们的多个原始细胞研究将建立一个进行性多发性脑震荡性CTE的小鼠模型。总体研究结果将为可靠地产生轻度TBI提供参数,
和情绪障碍,以促进未来的研究的神经生物学和神经遗传学基础的情绪和认知缺陷的轻度创伤性脑损伤,并开发有效的治疗方法。
项目成果
期刊论文数量(0)
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ANTON J. REINER其他文献
ANTON J. REINER的其他文献
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{{ truncateString('ANTON J. REINER', 18)}}的其他基金
A Mouse Model for Emotional Disorder Caused by Mild Traumatic Brain Injury
轻度创伤性脑损伤引起的情绪障碍小鼠模型
- 批准号:
8722052 - 财政年份:2013
- 资助金额:
$ 18.75万 - 项目类别:
Organization of the Cortical Projection to the Basal Ganglia
皮质投射到基底神经节的组织
- 批准号:
8044880 - 财政年份:2008
- 资助金额:
$ 18.75万 - 项目类别:
Organization of the Cortical Projection to the Basal Ganglia
皮质投射到基底神经节的组织
- 批准号:
7777251 - 财政年份:2008
- 资助金额:
$ 18.75万 - 项目类别:
Organization of the Cortical Projection to the Basal Ganglia
皮质投射到基底神经节的组织
- 批准号:
8266002 - 财政年份:2008
- 资助金额:
$ 18.75万 - 项目类别:
Organization of the Cortical Projection to the Basal Ganglia
皮质投射到基底神经节的组织
- 批准号:
7464384 - 财政年份:2008
- 资助金额:
$ 18.75万 - 项目类别:
Organization of the Cortical Projection to the Basal Ganglia
皮质投射到基底神经节的组织
- 批准号:
7559994 - 财政年份:2008
- 资助金额:
$ 18.75万 - 项目类别:
NEUROPATHOLOGY AND PATHOGENESIS OF HUNTINGTONS DISEASE
亨廷顿病的神经病理学和发病机制
- 批准号:
2411855 - 财政年份:1990
- 资助金额:
$ 18.75万 - 项目类别:
NEUROPATHOLOGY AND PATHOGENESIS OF HUNTINGTON' DISEASE
亨廷顿病的神经病理学和发病机制
- 批准号:
6457452 - 财政年份:1990
- 资助金额:
$ 18.75万 - 项目类别:
NEUROPATHOLOGY AND PATHOGENESIS OF HUNTINGTONS DISEASE
亨廷顿病的神经病理学和发病机制
- 批准号:
2445775 - 财政年份:1990
- 资助金额:
$ 18.75万 - 项目类别:
NEUROPATHOLOGY AND PATHOGENESIS OF HUNTINGTON' DISEASE
亨廷顿病的神经病理学和发病机制
- 批准号:
6126985 - 财政年份:1990
- 资助金额:
$ 18.75万 - 项目类别:
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