Connectome Analysis of the Nigrostriatal Neuronal Tract after Blast TBI

部署在阿富汗(持久自由行动；OEF)和伊拉克(行动)战争的军事人员 伊拉克自由(OIF)暴露于爆炸(BTBI)造成创伤性脑损伤(TBI)的风险很高 以及其他类型的头部损伤。此外，暴露在肩射武器的冲击波中可能会 影响大脑，即使在训练期间也是如此。所有严重程度的颅脑损伤都会导致部署后的慢性干扰 认知、行为、情感和身体功能。有大量证据表明创伤性脑损伤 脑损伤(TBI)导致多巴胺能系统的慢性缺陷，这可能有助于损伤后的认知功能。 这笔SPIRE赠款的目标是评估扩散磁共振成像和网络分析的使用情况，以 确定单次和重复模拟冲击波(激波管)暴露对 黑质纹状体相关纤维束。HTH-GFP报告大鼠将暴露于单一或重复的压力波 峰值压力为30psi或40psi。这些压力是基于初步数据显示的 40psi与30psi的空间记忆缺陷。一系列行为结果测试来评估运动，认知， 并测量与压力相关的功能。在模拟爆炸后4周，体外培养高清纤维 将结合网络拓扑分析执行跟踪(HDFT)，以表征 黑质和纹状体神经元网络通路。腹侧被盖区也将被评估。 初步的连接组分析表明，bTBI后中脑和纹状体的连通性受损。损失 BTBI后4周可初步观察到多巴胺能转运蛋白。初步成像 网络拓扑分析表明，黑质纹状体通路经历了较大的神经元网络重构。 BTBI后脑组织比海马区或杏仁核区强。多巴胺的免疫组织化学分析- 相关蛋白质将在成像后进行评估。总体假设是，暴露在不同的模拟环境中 冲击波超压将导致黑质纹状体完整性、多巴胺能标志物和 行为功能。该申请符合尖顶的目的，即支持高级调查人员寻求 在以前没有得到资助的领域探索新的研究方法。

Military personnel deployed to the wars in Afghanistan (Operation Enduring Freedom; OEF) and Iraq (Operation Iraqi Freedom; OIF) are at high risk of sustaining a traumatic brain injury (TBI) from exposures to a blast (bTBI) and other types of head injuries. Furthermore, exposure to blast waves from firing shoulder-fired weapons can affect the brain, even during training. TBI of all severities can result in chronic post-deployment disturbances of cognitive, behavioral, emotional, and physical functioning. There is extensive evidence that traumatic brain injury (TBI) produces chronic deficits in the dopaminergic system that may contribute to postinjury cognitive function. The goal of this SPiRE grant is to evaluate the use of diffusion MRI tractography and network analysis to determine the effects of single and repetitive simulated blast (shock tube) exposures on the integrity of nigrostriatal-associated tracts. hTH-GFP reporter rats will be exposed to single or repeated pressure waves at either peak pressure of 30psi or 40psi. These pressures are based on preliminary data demonstrating greater spatial memory deficits in the 40psi vs. 30psi. A battery of behavioral outcome tests to assess motor, cognitive, and stress-related function will be measured. At 4-weeks post-simulated blast, ex-vivo high-definition fiber tracking (HDFT) in conjunction with network topology analysis will be performed to characterize the integrity of substantia nigral and striatal neuronal network pathways. Ventral tegmental area tracts will also be assessed. Preliminary connectome analyses indicate that midbrain and striatal connectivity is impaired after bTBI. Loss of dopaminergic transporter protein was preliminarily observed after 4-week post-bTBI. Preliminary imaging network topological analysis showed that the nigrostriatal pathway underwent larger neuronal network re- organization after bTBI than hippocampal or amygdala regions. Immunohistochemical analyses of dopamine- related proteins will be assessed after imaging. The overall hypothesis is that exposure to varying simulated blast overpressures will result in graded reductions in nigrostriatal integrity, dopaminergic markers, and behavioral function. The application is in line with the SPiRE purpose to support senior investigators seeking to explore new research approaches in areas where they have not previously been funded.