SDR: Genomic analysis of blast tube induced TBI in mice

SDR：小鼠爆管诱发 TBI 的基因组分析

• 批准号: 10092813
• 负责人: Bruce A. Citron
• 金额: --
• 依托单位: VA NEW JERSEY HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10092813
• 关键词: Address; Affect; Anxiety; Behavior; Behavioral; Biochemistry; Blast Injuries; Blood; Blood - brain barrier anatomy; Brain; Brain Injuries; Cells; Disease; Exposure to; Eye; Foundations; Future; Gastrointestinal tract structure; Gene Expression; Genes; Genetic; Genetic Drift; Genetic Predisposition to Disease; Genetic Variation; Genomics; Genotype; Health; Histologic; Human Resources; Impairment; Individual; Inflammatory; Injury; International; Investigation; Kidney; Laboratories; Lead; Liver; Long-Term Effects; Lung; Memory; Messenger RNA; Military Personnel; Modeling; Molecular; Motor; Mouse Strains; Mus; Nerve Degeneration; Neuroglia; Neurons; Organ; Outcome; Pattern; Performance; Play; Positioning Attribute; Predisposition; Quantitative Reverse Transcriptase PCR; Recording of previous events; Recovery; Recovery of Function; Reporting; Research; Research Personnel; Resistance; Role; Services; Sex Differences; Source; Spleen; System; TBI treatment; Testing; Therapeutic; Tissue-Specific Gene Expression; Tissues; Traumatic Brain Injury; Traumatic Brain Injury recovery; Tube; Veterans; Western Blotting; Work; base; behavior test; behavioral outcome; blast exposure; cognitive performance; design; effective therapy; experience; experimental study; functional disability; functional outcomes; genetic information; improved; injury recovery; instrument; instrumentation; military veteran; mouse model; pressure; repaired; resilience; resistant strain; response; response to injury; sex; therapeutic target; transcriptome sequencing; traumatic event

Approximately 25% of the two million service personnel deployed since 2000 have reported receiving a traumatic brain injury (TBI). The vast majority of these are mild, and, in the military, due to exposure to blast waves from a variety of sources. Unfortunately, an effective treatment is still needed, meanwhile Veterans cope with long-term effects of impaired brain processing and neurodegeneration. A better understanding is needed to address the problems caused by TBI. Genetic predispositions to neuronal damage susceptibility versus predispositions to neuroprotective resilience and repair represent a understudied gap in our understanding of how to best treat the brain following a TBI. Moreover, as therapeutic approaches become more personalized, a robust understanding of the contributions of genetic background to TBI resilience and recovery is essential in order to develop solutions for our affected Veterans We will identify genes that affect the degree of blast-induced functional impairment and post-injury recovery by studying a set of model mouse strains that encompass most all of the genetic variations between laboratory strains. The injury model will utilize a well-established blast tube system designed to mimic pressure waves experienced during a field explosive detonation. A battery of behavioral tests will be performed at baseline prior to the injury and as long as 30 days after blast exposure to assess the role of genetics in recovery of functional outcomes, including different aspects of memory performance, anxiety, motor coordination, startle reactivity, and nesting. We will also compare TBI-induced region specific changes in markers of neurodegeneration and alterations in gene expression. We will also include examinations of other organs for blast-induced damage to see if the genetic factors influence the affects upon non-neuronal tissue. This research represents a multi-level examination of how certain genes influence blast-induced TBI and recovery. It will provide essential starting points for future investigations to understand how these genes play roles in the post-injury outcomes, to develop optimal models for blast studies, and to lead towards the definition of therapeutic targets that could be modulated to eventually improve the health of Veterans with histories of blast exposures.

自2000年以来部署的200万服务人员中约有25%报告说， 创伤性脑损伤（TBI）。其中绝大多数是温和的，在军队中， 因为暴露在各种爆炸源的冲击波下不幸的是，一种有效的治疗方法 与此同时，退伍军人科普大脑处理受损的长期影响， 和神经退化需要更好地理解，以解决 创伤性脑损伤神经元损伤易感性的遗传倾向与 神经保护性恢复和修复代表了我们理解的一个未充分研究的空白， 如何最好地治疗脑外伤后的大脑此外，随着治疗方法变得越来越多， 个性化，对遗传背景对TBI的贡献的强大理解 复原力和恢复是至关重要的，以便为我们受影响的退伍军人制定解决方案。 将确定影响爆炸引起的功能障碍程度和损伤后的基因， 通过研究一组模型小鼠品系，包括大多数所有的遗传恢复， 实验室菌株之间的差异。损伤模型将使用完善的爆炸管 一种模拟野外爆炸时产生的压力波的系统。一 将在受伤前的基线进行一系列行为测试， 在冲击波暴露后30天，以评估遗传学在功能结果恢复中的作用， 包括记忆表现、焦虑、运动协调、惊吓等不同方面 反应性和嵌套。我们还将比较TBI诱导的区域特异性标志物的变化， 神经退化和基因表达的改变。我们还将检查 其他器官的爆炸引起的损害，看看是否遗传因素影响的影响， 非神经组织这项研究代表了一个多层次的检查，如何某些基因 影响爆炸引起的TBI和恢复。它将为未来的发展提供重要的起点。 研究以了解这些基因如何在损伤后结果中发挥作用， 开发最佳模型进行爆炸研究，并导致治疗的定义 目标，可以调整，以最终改善退伍军人的健康与历史， 爆炸暴露