Technical enhancements for intracranial microdialysis

颅内微透析的技术改进

基本信息

批准号：
9789967
负责人：
Adrian C Michael
金额：
$ 17.99万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9789967
关键词：
Adopted Animal Model Anti-inflammatory Brain Brain Injuries Cessation of life Chemicals Chemistry Clinical Data Detection Dexamethasone Diagnosis Diagnostic Dialysis procedure Disease Evaluation Exhibits FDA approved Face Foundations Gliosis Glucose Hospitalization Human Inflammatory Injury Intensive Care Lesion Liquid substance Malignant Neoplasms Mass Spectrum Analysis Medical Membrane Metabolic Metabolic Marker Microdialysis Modification Molecular Monitor Neural Cell Adhesion Molecule L1 Neuroglia Operative Surgical Procedures Outcome Patient-Focused Outcomes Patients Pattern Recognition Performance Perfusion Peripheral Pharmaceutical Preparations Potassium Process Rattus Research Route Secondary to Site Source Statistical Methods Superoxide Dismutase Technology Therapeutic Traumatic Brain Injury Vegetative States Work base controlled cortical impact disability injured innovation nanoscale neurosurgery novel novel therapeutics potassium ion prevent sensor success surface coating tool

项目摘要

Intracranial microdialysis has been performed in human patients since the 1970s but has not yet been adopted or approved as a diagnostic technology. There is an urgent need for enhanced microdialysis technology with diagnostic capabilities. Microdialysis is the only existing technology with the demonstrated ability to detect two key chemical markers, glucose and potassium ion, of secondary brain injury in patients with severe traumatic brain injury. Diagnosis of secondary injury is critical because it is a major contributor to poor outcomes (severe disability, vegetative state, and death) even for patients who survive their injury, surgery, and several days of intensive care. Until recently, gliosis at the probe track has severely limited the performance capabilities of microdialysis. Adding dexamethasone to the perfusion fluid, however, has proven a simple yet highly effective approach to suppressing gliosis. Dexamethasone has enabled us to recently detect aberrations of glucose and potassium in the cortex of the rat brain 11 days after inducing an injury by controlled cortical impact. Herein, we propose to explore three additional novel and significant technical enhancements for intracranial microdialysis that build on our recent successes. First, we propose to explore nano-scale modifications of the dialysis membrane as an alternative to dexamethasone, because circumstances may arise that preclude the use of dexamethasone. Second, we propose to explore glucose delivery as a means to reverse glucose deficits in the rat brain after controlled cortical impact: this work will establish the foundation for a novel therapy for secondary brain injury. Third, in a search for novel chemical markers for secondary injury, we will explore mass spectrometric analysis of brain dialysate as a source of orthogonal chemical information from the brain.

自1970年代以来，人类患者已经进行了颅内微透析，但尚未进行被采用或批准为诊断技术。迫切需要增强具有诊断能力的微透析技术。微透析是唯一现有的具有检测两个关键化学标记物的技术，葡萄糖和钾离子，严重创伤性脑损伤患者的继发性脑损伤。诊断次要伤害至关重要，因为它是导致不良结果的主要因素（严重的残疾，植物状态和死亡）即使对于在受伤，手术和几天生存的患者中也是如此重症监护。直到最近，探针轨道的神经胶质严重限制了性能微透析的能力。然而，在灌注液中添加地塞米松已被证明是简单但高效抑制神经胶质的方法。地塞米松使我们能够最近发现在大鼠脑皮层中发现葡萄糖和钾的像差11天后通过受控的皮质影响诱导损伤。本文中，我们建议探索三种其他新颖和重大的技术增强功能颅内微透析基于我们最近的成功。首先，我们建议探索透析膜的纳米级修饰是地塞米松的替代品，因为可能会出现排除地塞米松使用的情况。其次，我们建议探索葡萄糖递送，作为控制皮质后逆转大鼠大脑中葡萄糖缺陷的一种手段影响：这项工作将为继发性脑损伤的新疗法奠定基础。第三，在寻找用于继发性损伤的新型化学标志物中，我们将探索质量脑透析酸盐的光谱分析是从脑。