The effects of glycemic control on post-traumatic brain metabolism

动物研究表明，脑创伤后存在氧化和葡萄糖代谢障碍 损伤(TBI)，以代谢抑制为显著特征。我们最近的人体研究已经 证实了两个相关的发现：1)脑损伤后存在较长时间的代谢抑制 2)在这种代谢抑制过程中，细胞外葡萄糖浓度往往较低。持续时间 细胞外葡萄糖浓度低的程度是神经预后的独立预测因素。在… 同时，许多实验和临床研究表明，全身性高血糖 对人类颅脑损伤后的预后产生不利影响。因此，目前的护理标准要求使用胰岛素来 维持正常血糖。然而，人们对血糖控制对大脑新陈代谢的影响知之甚少。 也没有通过严格的血糖控制来限制脑外伤后血糖供应的潜在不良影响。我们有 证明胰岛素导致细胞外葡萄糖减少和细胞外葡萄糖增加。 谷氨酸(Vespa，2006)暗示了可能的不良反应。因此，关于On的争论是存在的 如何在脑外伤中最好地管理全身血糖浓度。考虑到潜在的治疗意义， 我们迫切需要更好地了解血糖控制对脑损伤后脑代谢的影响。 该项目建议研究葡萄糖可获得性限制(血清葡萄糖)的零假设 浓度)通过使用受控胰岛素来降低大脑葡萄糖和氧化代谢率 输液以达到正常的血糖浓度(80-110 mg/dl)。此外，我们建议测试一个 二次假设：将血糖降至正常浓度将导致微透析 联合应用受试者内和脑外伤后患者的代谢窘迫标志物 随机交叉研究设计。这个项目与这个项目中的项目1、2和4错综复杂地相互关联 PPG。

Animal studies have demonstrated a disturbance in oxidative and glucose metabolism after traumatic brain injury (TBI), with depression of metabolism being a significant feature. Our recent human studies have demonstrated two related findings: 1) There is a prolonged period of metabolic depression after brain injury and 2) extracellular glucose concentrations are frequently low during this metabolic depression. The duration and extent of low extracellular glucose concentration are independent predictors of neurologic outcome. At the same time, many experimental and clinical studies have demonstrated that systemic hyperglycemia adversely affects outcome after human TBI. Hence, the current standard of care requires the use of insulin to maintain nomoglycemia. However, little is known about the effects of glycemic control on brain metabolism nor the potential adverse effects of limiting glucose supply through strict glycemic control after TBI. We have demonstrated that insulin results in reduction in extracellular glucose and an increase in extracellular glutamate (Vespa, 2006) suggesting a possible adverse effect. Thus, there exists a controversy about on how best to manage systemic glucose concentrations in TBI. Given the potential therapeutic implications, there is a profound need to better understand the effects of glycemic control on brain metabolism after TBI. This project proposes to study the null hypothesis that limitation of glucose availability (serum glucose concentrations) reduces the rates of cerebral glucose and oxidative metabolism, by using a controlled insulin infusion to achieve normal serum glucose concentrations (80-110 mg/dl). In addition, we propose to test a secondary hypothesis that reduction of serum glucose to normal concentrations will result in microdialysis markers of metabolic distress in post-traumatic brain injured patients using a combined within-subjects and randomized cross over study design. This project is intricately inter-related with projects 1, 2 and 4 of this PPG.