Enhanced Bedside Microdialysis for TBI

本项目的目标是提供增强床旁微透析，用于监测严重创伤性脑损伤神经外科手术后重症监护患者的脑间质葡萄糖和K+水平。最终目标是在真实的时间内量化由扩散性去极化（SD）引起的代谢危机的幅度和持续时间，SD在受伤的大脑中普遍存在，并且是导致患者预后不良（包括严重残疾、植物人状态和死亡）的继发性损伤的基础。 皮质电图（ECoG）显示，受损的大脑对SD高度敏感，但ECoG并不是用来检测或量化SD对大脑代谢的影响。SD后组织的复极化需要如此大量的能量，以至于葡萄糖水平可能被驱动到危险的低水平，特别是在其中再供应葡萄糖的血流可能受到损害的受伤组织中。通过量化损伤半影区低血糖发作的幅度和持续时间，我们将提供继发性损伤的诊断。目前缺乏诊断技术是一个障碍，治疗策略管理继发性损伤。尽管临床微透析已被证明有能力量化SD后的代谢危机，但迫切需要大量的技术改进。手术后需要对患者进行10天的监测，但由于探针轨道处的神经胶质增生，常规微透析在2-3天后的价值有限。Michael实验室的临床前研究表明，地塞米松（一种强效抗炎剂）的后透析是一种简单而高效的方法，可将功能性微透析延长至至少10天。Boutelle集团开发的新技术将进一步增强微透析，用于连续、快速、在线、无线、自动化的葡萄糖和K+测定，时间分辨率为1分钟。在神经外科专家的帮助下，我们建议将增强微透析转化为严重创伤性脑损伤患者，以确定化学记录与患者结局之间相关性的统计学意义，并继续对我们的增强微透析方法进行临床前改进。

The goal of this project is to deliver enhanced bedside microdialysis for monitoring interstitial brain glucose and K+ levels in patients in intensive care after neurosurgery for severe traumatic brain injury. The ultimate objective is to quantify, in real time, the magnitude and duration of metabolic crises caused by spreading depolarization (SD), which are prevalent in the injured brain and underlie the secondary injury responsible for poor patient outcomes, including severe disability, vegetative state, and death. Electrocorticography (ECoG) shows that the injured brain is highly susceptible to SD but ECoG is not designed to detect or quantify the impact of SD on brain metabolism. Repolarization of tissues after SD requires such vast amounts of energy that glucose levels can be driven dangerously low, especially in injured tissue where blood flow to resupply glucose may be compromised. By quantifying the magnitude and duration of hypoglycemic episodes in the injury penumbra, we will deliver a diagnostic for secondary injury. The present absence of diagnostic technology is a roadblock to therapeutic strategies for managing secondary injury. Although clinical microdialysis has the demonstrated ability to quantify metabolic crisis after SD, substantial technical enhancements are urgently needed. Patients need to be monitored for 10 days after surgery but, due to gliosis at the probe track, conventional microdialysis is of limited value after 2-3 days. Preclinical studies in the Michael laboratory have demonstrated that retrodialysis of dexamethasone, a potent anti-inflammatory agent, is a simple yet highly effective means of extending functional microdialysis to at least 10 days. Microdialysis will be further enhanced by new technology, developed by the Boutelle group, for continuous, rapid, on-line, wireless, automated assays of glucose and K+ with 1-min temporal resolution. With the aid of expert neurosurgeons, we propose to translate enhanced microdialysis to patients with severe traumatic brain injury, to determine the statistical significance of correlations between chemical recordings and patient outcomes, and to continue the preclinical refinement of our enhanced microdialysis approaches.