Enhanced Bedside Microdialysis for TBI

该项目的目标是提供增强的床边微透析，用于监测重型颅脑损伤神经外科手术后重症监护患者的脑间质葡萄糖和钾水平。最终目标是实时量化扩散性去极化(SD)引起的代谢危机的程度和持续时间，扩散性去极化普遍存在于受损的大脑中，是导致患者预后不良的继发性损伤的基础，包括严重残疾、植物状态和死亡。 皮层脑电图术(ECoG)显示，受损的大脑对SD高度敏感，但ECoG的设计不是为了检测或量化SD对大脑代谢的影响。SD后组织的复极需要如此巨大的能量，以至于葡萄糖水平可能被压低到危险的水平，特别是在受伤的组织中，补充葡萄糖的血流可能会受到影响。通过量化损伤半影区低血糖发作的程度和持续时间，我们将提供对继发性损伤的诊断。目前缺乏诊断技术是管理继发性损伤的治疗策略的障碍。尽管临床微透析已经证明有能力量化SD后的代谢危机，但迫切需要实质性的技术改进。患者需要在术后10天内接受监测，但由于探头轨迹处的胶质细胞增多，传统的微透析在2-3天后价值有限。迈克尔实验室的临床前研究表明，地塞米松是一种有效的抗炎剂，它的反透析是将功能性微透析延长到至少10天的一种简单而高效的方法。由Boutelle集团开发的新技术将进一步加强微透析，以实现1分钟时间分辨率的连续、快速、在线、无线、自动化的葡萄糖和钾分析。在专家神经外科医生的帮助下，我们建议将增强型微透析转化为严重创伤性脑损伤患者，确定化学记录与患者预后之间的相关性的统计学意义，并继续我们的增强型微透析方法的临床前改进。

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.