The effects of glycemic control on post-traumatic brain metabolism

动物研究表明，脑外伤后氧化和葡萄糖代谢紊乱 创伤性脑损伤（TBI），代谢抑制是一个重要特征。我们最近的人类研究 结果表明：1）脑损伤后存在较长时间的代谢抑制 和2）在这种代谢抑制期间，细胞外葡萄糖浓度通常较低。持续时间 和细胞外低葡萄糖浓度的程度是神经学结果的独立预测因子。在 同时，许多实验和临床研究表明，全身性高血糖 对人TBI后的结果产生不利影响。因此，目前的护理标准要求使用胰岛素， 维持血糖正常。然而，人们对血糖控制对大脑代谢的影响知之甚少 也没有通过TBI后严格血糖控制限制葡萄糖供应的潜在不良影响。我们有 表明胰岛素导致细胞外葡萄糖的减少和细胞外葡萄糖的增加。 谷氨酸盐（Vespa，2006），提示可能存在不良反应。因此，存在着关于 如何最好地管理TBI中的全身葡萄糖浓度。考虑到潜在的治疗意义， 非常需要更好地理解血糖控制对TBI后脑代谢的影响。 本项目拟研究葡萄糖可利用性（血清葡萄糖）的限制 浓度）降低脑葡萄糖和氧化代谢的速率，通过使用受控的胰岛素， 输注以达到正常血清葡萄糖浓度（80-110 mg/dl）。此外，我们建议测试一个 次要假设：血清葡萄糖降至正常浓度将导致微透析 使用受试者内和 随机交叉研究设计。该项目与本项目的项目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.