Amygdala Response to Experimental Traumatic Brain Injury

杏仁核对实验性脑外伤的反应

基本信息

批准号：
6953126
负责人：
JONATHAN LIFSHITZ
金额：
$ 5.15万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
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/6953126
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

项目摘要

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，每年有50万人每年遭受创伤性脑损伤（TBI），使TBI成为死亡和残疾的主要原因。随着事故现场和急诊护理的改善，死亡率下降了，有2-4万人幸免于难。患者和患者家庭主要抱怨脑震荡综合征，涉及认知，侵略性，情绪稳定，抑制和人格的改变。实际上，脑震荡综合征类似于杏仁核切除或变性的症状。鉴于这些伤害后的缺陷，该提议的项目启动了实验，集中于定义脑抑制综合征的一部分症状是否是在小鼠脑损伤的临床相关横向液体打击模型中对杏仁核的损害介导的。中心假设是：实验性TBI双侧损坏杏仁核。三个目的检验了假设：（1）使用条件恐惧证明依赖杏仁核依赖性的认知缺陷，（2）使用基于设计的体制的基底外侧复合物和杏仁核的中心核来量化选择性神经元损失，并使用设计基于设计的定制和（3）用于评估和药理学的功能性循环级，以进行amygdala的核心。现场记录。在行为，解剖学和功能方面，调查TBI后研究杏仁核病理学的系统方法可以揭示脑抑制后综合征的机制。除创伤后应激障碍和精神病外，这项研究工作可能导致对原本健康的脑部受伤人群中情感障碍的新治疗。