TBI-Induced Cerebral Metabolic Depression and Recovery

TBI 引起的脑代谢抑制和恢复

• 批准号: 8284886
• 负责人: DAVID A HOVDA
• 金额: $ 6.01万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8284886
• 关键词: Acute; Address; Animals; Basic Science; Biochemical Pathway; Brain; Brain Injuries; Cell Death; Cell physiology; Cells; Cerebrum; Clinical; Complement; Consumption; Critical Care; Data; Destinations; Development; Distress; Event; Experimental Designs; Future; Genetic Crossing Over; Glucose; Housing; Human; Image; Injury; Insulin; Intensive Care Units; Intervention; Ketones; Laboratories; Lead; Measures; Mental Depression; Metabolic; Metabolic Pathway; Metabolism; Outcome; Patient Care; Patients; Pyruvate; Rattus; Recovery; Recovery of Function; Research; Research Personnel; Role; Secondary to; Security; Seizures; Serum; Techniques; Tissues; Traumatic Brain Injury; cell injury; controlled cortical impact; design; injured; man; neurochemistry; postnatal; programs; spreading depression

The central theme of this proposal is to identify the metabolic destination of cerebral glucose taken up after traumatic brain injury (TBI), thereby discovering alternative metabolic pathways receptive to interventions (metabolic therapy) to enhance cellular and functional recovery and ultimately change the future of TBI patient management. Two basic science projects will explore these fundamental issues, and are designed to lead as well as complement two clinical projects. Project 1 (Dr. Richard Sutton) addresses the administration of glucose and pyruvate following cortical controlled impact in the rat to examine their impact on cerebral metabolism, cellular protection and outcome. Project 2 (Dr. Mayumi Prins) will study postnatal day 35 and postnatal day 90 rats using the developmental maturation of fuel transporters as an independent variable. Transporters for the fuels glucose, lactate and ketones will be measured in terms of their expression and function. The focus of ketone metabolism is a unique feature in this project as it not only addresses the effect on outcome, but also rigorously studies the appropriate biochemical pathways. Project 3 (Dr. Paul Vespa) addresses the topic of glucose substrate supply for human TBI patients primarily from the perspective of management of serum glucose concentration. Using different levels of insulin therapy, the effect on global and regional cerebral metabolism will be compared to neurochemical and anatomical markers of cell distress. In a creative cross over experimental design preliminary data will be collected for a future clinical trail. Project 4 (Dr. Neil Martin) will utilize the Kety-Schmidt technique to address how glucose is consumed differently in the human injured brain. The investigators within this program will determine the change in the consumption of cerebral glucose, the effects of changes in transporters, and the effects of enhancing or restricting glucose delivery and the potential use of alternative fuels. This program project will be housed within the UCLA Brain Injury Research Center (Dr. David A. Hovda, Director) so as to assure appropriate imaging, administrative and laboratory support.

该提案的中心主题是确定创伤性脑损伤（TBI）后脑葡萄糖的代谢目的地，从而发现接受干预（代谢治疗）的替代代谢途径，以增强细胞和功能恢复，并最终改变TBI患者管理的未来。两个基础科学项目将探索这些基本问题，并旨在领导和补充两个临床项目。项目1（Richard萨顿博士）研究了大鼠皮质受控撞击后葡萄糖和丙酮酸盐的给药，以检查其对脑代谢、细胞保护和结局的影响。项目2（Mayumi Prins博士）将使用燃料转运蛋白的发育成熟作为自变量研究出生后35天和出生后90天的大鼠。将测量燃料葡萄糖、乳酸盐和酮的转运蛋白的表达和功能。对酮代谢的关注是该项目的独特之处，因为它不仅解决了对结果的影响，而且还严格研究了适当的生化途径。项目3（Paul Vespa博士）主要从血清葡萄糖浓度管理的角度探讨了TBI患者葡萄糖底物供应的主题。使用不同水平的胰岛素治疗，对整体和局部脑代谢的影响将与细胞窘迫的神经化学和解剖学标志物进行比较。在一个创造性的交叉实验设计中，将收集初步数据用于未来的临床试验。项目4（Neil Martin博士）将利用Kety-Schmidt技术来解决葡萄糖在人类受伤大脑中的不同消耗方式。该项目的研究人员将确定脑葡萄糖消耗的变化、转运蛋白变化的影响、增强或限制葡萄糖输送的影响以及替代燃料的潜在使用。该项目将设在加州大学洛杉矶分校脑损伤研究中心（大卫A。Hovda，主任），以确保适当的成像，行政和实验室支持。