Cerebral Lactate Metabolism Following Human Traumatic Brain Injury

人类脑外伤后脑乳酸代谢

• 批准号: 7257760
• 负责人: NEIL A. MARTIN
• 金额: $ 19.87万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7257760
• 关键词: Acidosis; Acute Brain Injuries; Address; Affect; Area; Brain; Brain Hypoxia-Ischemia; Brain Injuries; Carbohydrates; Carbon; Cell Death; Cell Respiration; Cells; Cerebral Ischemia; Cerebrum; Characteristics; Chemicals; Clinical; Clinical Research; Condition; Deuterium; Doctor of Philosophy; Energy Metabolism; Enzymes; Failure; Financial compensation; Foundations; Functional disorder; Future; Glucose; Glycolysis; Hour; Human; Infusion procedures; Injury; Intracranial Hemorrhages; Ischemic Stroke; Isotope Labeling; Isotopes; Laboratories; Magnetic Resonance Spectroscopy; Measurement; Measures; Medical center; Metabolic; Metabolic Pathway; Metabolism; Microdialysis; Monitor; Neurons; Nutritional Support; Outcome; Patients; Protocols documentation; Rate; Recovery; Research Personnel; Role; Solutions; Standards of Weights and Measures; Techniques; Tracer; Trauma; Traumatic Brain Injury; Waste Products; base; carbohydrate metabolism; cell injury; concept; glucose metabolism; glucose uptake; injured; metabolic abnormality assessment; mitochondrial dysfunction; novel strategies; oxidation; uptake

DESCRIPTION (provided by applicant): This project is focused on our recent demonstration that traumatic brain injury (TBI), after the first 12-24 hours, is typically accompanied by significant cerebral lactate uptake and utilization. This finding is not encompassed by contemporary concepts of post-traumatic cerebral metabolic dysfunction, and cannot easily be reconciled with the view that lactate accumulation and acidosis are common causes of cell death after trauma. Lactate is fundamental to the understanding of traumatic pathobiology. Furthermore, it is becoming a key component of neuro-monitoring through cerebral microdialysis; and it is regarded as an important marker of cerebral ischemia in arterio-jugular measurements, and MR spectroscopy. Because of the important yet incompletely understood role of lactate in metabolic dysfunction after TBI, we propose to study its uptake by the brain, and its metabolism. Our main hypothesis is that lactate is taken and oxidized in the brain after traumatic brain injury. We also intend to study cerebral glucose metabolism in an analogous and parallel fashion, to understand more completely the alterations in carbohydrate metabolism induced by injury. To answer the key scientific questions addressed in this project, we plan to take the novel approach of using deuterium (D2) and carbon (13C-)) glucose and lactate isotope tracer metabolic techniques to study cerebral metabolism in brain injury patients. Our specific aims are: 1. To determine the extent to which brain glucose uptake, glycolysis, and glucose oxidation are affected (suppressed) after TBI. 2. To determine the extent to which brain lactate uptake and oxidation are affected (augmented) after TBI. 3. To determine the extent to which the rates of lactate and glucose oxidation correlate with clinical characteristics and outcome after TBI. If the studies proposed in this project confirm that lactate is a viable fuel for the injured brain, the next step will be to consider lactate administration as "metabolic therapy" for brain injury. We have previously shown that the brain takes up the chemical called lactate after traumatic brain injury. This project will determine if the brain is using the lactate to help it recover after injury. If the studies proposed in this project confirm that lactate helps the injured brain, the next step will be to consider lactate administration as new "metabolic therapy" for brain injury.

描述（由申请人提供）：该项目的重点是我们最近的证明，即创伤性脑损伤 (TBI) 在最初 12-24 小时后通常会伴随着大量的脑乳酸吸收和利用。这一发现并不包含在创伤后脑代谢功能障碍的当代概念中，并且不能轻易地与乳酸蓄积和酸中毒是创伤后细胞死亡的常见原因的观点相一致。乳酸是理解创伤病理学的基础。此外，它正在成为通过脑微透析进行神经监测的关键组成部分；它被认为是颈动脉测量和磁共振波谱学中脑缺血的重要标志物。由于乳酸在 TBI 后代谢功能障碍中的重要但尚未完全了解的作用，我们建议研究大脑对乳酸的摄取及其代谢。我们的主要假设是，脑外伤后，乳酸在大脑中被吸收并氧化。我们还打算以类似和平行的方式研究脑葡萄糖代谢，以更全面地了解损伤引起的碳水化合物代谢的变化。为了回答该项目中解决的关键科学问题，我们计划采用使用氘（D2）和碳（13C-））葡萄糖和乳酸同位素示踪代谢技术的新方法来研究脑损伤患者的脑代谢。我们的具体目标是： 1. 确定 TBI 后大脑葡萄糖摄取、糖酵解和葡萄糖氧化受到影响（抑制）的程度。 2. 确定 TBI 后大脑乳酸摄取和氧化受到影响（增强）的程度。 3. 确定乳酸和葡萄糖氧化速率与 TBI 后临床特征和结果的相关程度。如果该项目提出的研究证实乳酸是受伤大脑的可行燃料，那么下一步将考虑将乳酸给药作为脑损伤的“代谢疗法”。我们之前已经证明，脑外伤后大脑会吸收一种叫做乳酸的化学物质。该项目将确定大脑是否使用乳酸来帮助其在受伤后恢复。如果该项目提出的研究证实乳酸有助于受伤的大脑，下一步将考虑将乳酸给药作为脑损伤的新“代谢疗法”。