TBI-Induced Cerebral Metabolic Depression and Recovery

TBI 引起的脑代谢抑制和恢复

• 批准号: 8460073
• 负责人: DAVID A HOVDA
• 金额: $ 119.25万
• 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 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8460073
• 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.

该提案的中心主题是确定创伤性脑损伤（TBI）后吸收的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 的未来患者管理。两个基础科学项目将探讨这些基本问题，旨在引导和补充两个临床项目。项目 1（Richard Sutton 博士）致力于在大鼠皮质受控影响后施用葡萄糖和丙酮酸，以检查它们对脑代谢、细胞保护和结果的影响。项目 2（Mayumi Prins 博士）将使用燃料转运蛋白的发育成熟度作为自变量来研究出生后第 35 天和出生后第 90 天的大鼠。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一个独特特征，因为它不仅解决对结果的影响，而且还严格研究适当的生化途径。项目 3（Paul Vespa 博士）主要从血糖浓度管理的角度讨论人类 TBI 患者的葡萄糖底物供应主题。使用不同水平的胰岛素治疗，对整体和区域脑代谢的影响将与细胞窘迫的神经化学和解剖标志物进行比较。在创造性的交叉实验设计中，将为未来的临床试验收集初步数据。项目 4（尼尔·马丁博士）将利用 Kety-Schmidt 技术来解决人类受伤大脑中葡萄糖消耗方式的不同问题。该计划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。该计划项目将设在加州大学洛杉矶分校脑损伤研究中心（主任 David A. Hovda 博士）内，以确保提供适当的成像、行政和实验室支持。

项目成果

Cerebral metabolism following traumatic brain injury: new discoveries with implications for treatment.

• DOI: 10.3389/fnins.2014.00408
• 发表时间: 2014
• 期刊: Frontiers in neuroscience
• 影响因子: 4.3
• 作者: Brooks GA;Martin NA
• 通讯作者: Martin NA

Metabolic Response of Pediatric Traumatic Brain Injury.

• DOI: 10.1177/0883073814549244
• 发表时间: 2016-01
• 期刊: Journal of child neurology
• 影响因子: 1.9
• 作者: Prins ML;Matsumoto J
• 通讯作者: Matsumoto J

Influence of Glycemic Control on Endogenous Circulating Ketone Concentrations in Adults Following Traumatic Brain Injury.

• DOI: 10.1007/s12028-016-0313-3
• 发表时间: 2017-04
• 期刊: Neurocritical care
• 影响因子: 3.5
• 作者: Wolahan SM;Prins ML;McArthur DL;Real CR;Hovda DA;Martin NA;Vespa PM;Glenn TC
• 通讯作者: Glenn TC

Endogenous Nutritive Support after Traumatic Brain Injury: Peripheral Lactate Production for Glucose Supply via Gluconeogenesis.

• DOI: 10.1089/neu.2014.3482
• 发表时间: 2015-06-01
• 期刊: Journal of neurotrauma
• 影响因子: 4.2
• 作者: Glenn TC;Martin NA;McArthur DL;Hovda DA;Vespa P;Johnson ML;Horning MA;Brooks GA
• 通讯作者: Brooks GA

The pathophysiology of traumatic brain injury at a glance.

• DOI: 10.1242/dmm.011585
• 发表时间: 2013-11
• 期刊: Disease models & mechanisms
• 影响因子: 4.3
• 作者: Prins M;Greco T;Alexander D;Giza CC
• 通讯作者: Giza CC