Technical enhancements for intracranial microdialysis

颅内微透析的技术改进

• 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
• 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

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20世纪70年代以来，颅内微透析一直在人类患者身上进行，但至今还没有。 被采纳或批准为诊断技术。迫切需要加强 具有诊断能力的微透析技术。微透析是目前唯一存在的 具有检测葡萄糖和钾这两个关键化学标志物的能力的技术 重型颅脑损伤患者继发性脑损伤的临床意义。诊断 继发性损伤是至关重要的，因为它是造成不良结局(严重残疾、 植物状态和死亡)，甚至对于那些在受伤、手术和几天内幸存下来的患者 重症监护室。直到最近，探测器轨道上的胶质增生严重限制了性能。 微透析的能力。然而，将地塞米松添加到灌注液中已被证明是 简单但高效的方法来抑制胶质细胞增多症。地塞米松使我们能够 最近检测到11天后大鼠大脑皮质中葡萄糖和钾的异常 通过受控的皮质撞击而导致的伤害。 在这里，我们建议探索另外三个新颖和重要的技术增强，以 在我们最近成功的基础上发展起来的颅内微透析。首先，我们建议探索 作为地塞米松替代品的透析膜的纳米级修饰，因为 可能会出现阻止使用地塞米松的情况。第二，我们建议探索 葡萄糖输送作为一种逆转控制皮质后大鼠脑内葡萄糖缺乏的手段 影响：这项工作将为继发性脑损伤的新疗法奠定基础。 第三，在寻找新的二次损伤化学标志物的过程中，我们将探索 脑透析液作为正交化学信息源的光谱分析 大脑。