Cerebral Lactate Metabolism Following Human Traumatic 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）后的第一个12-24小时，通常伴随着显着的脑乳酸摄取和利用。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，也不容易与乳酸盐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。乳酸盐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;并且它被认为是动脉-颈静脉测量和MR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不完全理解的作用，我们建议研究其在脑中的摄取及其代谢。我们的主要假设是，脑外伤后，乳酸在脑中被摄取和氧化。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糖代谢的改变。为了回答这个项目中的关键科学问题，我们计划采用新的方法，使用氘（D2）和碳（13 C-））葡萄糖和乳酸同位素示踪代谢技术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后临床特征和结局相关的程度。如果本项目中提出的研究证实乳酸盐是受伤大脑的可行燃料，下一步将考虑将乳酸盐给药作为脑损伤的“代谢疗法”。我们之前已经证明，大脑在创伤性脑损伤后会吸收一种叫做乳酸的化学物质。这个项目将确定大脑是否在使用乳酸盐来帮助它在受伤后恢复。如果本项目中提出的研究证实乳酸盐有助于受伤的大脑，下一步将考虑将乳酸盐给药作为脑损伤的新“代谢疗法”。

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.