TBI-Induced Cerebral Metabolic Depression and Recovery

TBI 引起的脑代谢抑制和恢复

• 批准号: 8246433
• 负责人: DAVID A HOVDA
• 金额: $ 123.57万
• 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 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8246433
• 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; 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; metabolic depression; 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.

该提案的主要主题是确定创伤性脑损伤（TBI）摄入的脑葡萄糖的代谢目的地，从而发现接受干预措施（代谢疗法）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讨这些基本问题，并旨在领导和补充两个临床项目。项目1（理查德·萨顿（Richard Sutton）博士）解决了大鼠皮质控制影响后的葡萄糖和丙酮酸的给药，以检查其对脑代谢，细胞保护和预后的影响。项目2（Mayumi Prins博士）将使用燃料转运蛋白作为独立变量来研究产后第35天和产后90大鼠。燃料葡萄糖，乳酸和酮的转运蛋白将根据其表达和功能进行测量。酮代谢的重点是该项目的独特特征，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）介绍了人类TBI患者的葡萄糖底物供应主题，主要是从血清葡萄糖浓度管理的角度来解决。使用不同水平的胰岛素治疗，将将对全球和区域大脑代谢的影响与细胞遇险的神经化学和解剖学标记进行比较。在一个创造性的十字架上，将收集实验设计的初步数据，以进行未来的临床步道。项目4（Neil Martin博士）将利用KETY-SCHMIDT技术来解决人体受伤大脑中葡萄糖的消耗方式。该计划中的研究人员将决定脑葡萄糖消耗的变化，转运蛋白变化的影响以及增强或限制葡萄糖递送的影响以及替代燃料的潜在使用。该计划项目将安置在UCLA脑损伤研究中心（主管David A. Hovda博士）中，以确保适当的成像，行政和实验室支持。