Amygdala Response to Experimental Traumatic Brain Injury

杏仁核对实验性脑外伤的反应

• 批准号: 6837236
• 负责人: JONATHAN LIFSHITZ
• 金额: $ 4.89万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-20 至 2006-09-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6837236
• 关键词: amygdala; behavioral /social science research tag; brain injury; cognition disorders; conditioning; emotions; fear; laboratory mouse; neural plasticity; neuropathology; postdoctoral investigator; stereotaxic techniques; trauma

DESCRIPTION (provided by applicant): In the United States alone, 500,000 people suffer traumatic brain injury (TBI) annually, making TBI a leading cause of death and disability. With improved accident scene and emergency care, mortality rates have declined, with 2-4 million people surviving TBI. Patients and patient families chiefly complain about post-concussive syndrome, involving alterations in cognition, aggression, emotional stability, disinhibition, and personality. In fact, post-concussive syndrome resembles the symptoms of amygdala resection or degeneration. In light of these post-injury deficits, the proposed project initiates experimentation focused on whether a subset of symptoms that define post-concussion syndrome are mediated by damage to the amygdala in a clinically relevant lateral fluid percussion model of brain injury in the mouse. The central hypothesis is: experimental TBI damages the amygdala bilaterally. Three aims test the hypothesis: (1) to demonstrate amygdala-dependent cognitive deficits using conditioned fear, (2) to quantify selective neuronal loss in the basolateral complex and central nucleus of the amygdala using design-based stereology, and (3) to evaluate and pharmacologically modulate functional circuitry and synaptic plasticity in the amygdala-hippocampal circuit using extracellular field recordings. The systems approach to investigate amygdala pathology after TBI, in terms of behavior, anatomy and function, can reveal mechanisms underlying post-concussion syndrome. This research effort may lead to novel treatments for the affective disorders in an otherwise healthy brain-injured population, in addition to post-traumatic stress disorder and psychosis.

描述（由申请人提供）： 仅在美国，每年就有 50 万人遭受创伤性脑损伤 (TBI)，使 TBI 成为死亡和残疾的主要原因。随着事故现场和急救护理的改善，死亡率有所下降，有 2-400 万人在 TBI 中幸存。患者和患者家属主要抱怨脑震荡后综合症，包括认知、攻击性、情绪稳定性、抑制解除和人格的改变。事实上，脑震荡后综合症类似于杏仁核切除或变性的症状。鉴于这些损伤后缺陷，拟议的项目启动了实验，重点关注定义脑震荡后综合征的一组症状是否是由临床相关的小鼠脑损伤侧向液体冲击模型中杏仁核的损伤介导的。中心假设是：实验性 TBI 损害双侧杏仁核。三个目标检验该假设：（1）使用条件性恐惧来证明杏仁核依赖性认知缺陷，（2）使用基于设计的体视学来量化基底外侧复合体和杏仁核中央核中的选择性神经元损失，以及（3）评估并利用细胞外场记录对杏仁核-海马回路中的功能回路和突触可塑性进行药理学调节。从行为、解剖和功能方面研究 TBI 后杏仁核病理学的系统方法可以揭示脑震荡后综合症的机制。除了创伤后应激障碍和精神病之外，这项研究工作可能会为健康的脑损伤人群的情感障碍带来新的治疗方法。