Enhanced Microdialysis for CSD Monitoring

用于 CSD 监测的增强型微透析

• 批准号: 9035808
• 负责人: Adrian C Michael
• 金额: $ 21.75万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9035808
• 关键词: Address; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Beds; Blood flow; Brain; Brain Injuries; Cessation of life; Clinical; Data; Development; Dexamethasone; Diagnostic; Dose; Environment; Epidemic; Event; Gliosis; Glucose; Goals; Human; Implant; Injury; Institutional Review Boards; Intensive Care; Ischemia; Lead; Letters; Measurement; Medical Staff; Metabolic; Microdialysis; Migraine; Monitor; Neurons; Outcome; Patient Care; Patients; Penetration; Performance; Rattus; Recurrence; Reporting; Risk; Role; Route; Safety; Sampling; Secondary to; Severities; Side; Site; Spreading Cortical Depression; Technology; Time; Tissues; Traumatic Brain Injury; Vegetative States; brain tissue; clinically relevant; controlled cortical impact; deprivation; disability; improved; injured; interstitial; member; microsensor; public health relevance; response; spreading depression

 DESCRIPTION (provided by applicant): Brain injury gives rise to the phenomenon of cortical spreading depression. In healthy brain, spreading depressions are associated with migraine but are not known to cause brain damage. In the injured brain, recurrent spreading depressions lead to secondary brain injury and correlate significantly with poor patient outcomes including death, vegetative state, or severe disability 6 months after the primary injury. Microdialysis in patients with brain injury shows that spreading depressions deplete brain glucose, reflecting the sudden and intense demand for energy to drive ATP-dependent repolarization of brain tissue after the depolarization wave passes. Glucose delivery via the blood flow fails to keep pace with the demand and brain tissue becomes glucose deprived. This glucose deprivation is implicated in secondary injury to the at-‐risk penumbral tissue, resulting in expansion of the injury core. At present, clinical microdialysis is not used to assess the metabolic severity of spreading depressions due to variability in the results. The objective of this project is to develop, in experimental animals, "dexamethasone-enhanced microdialysis" as an approach to eliminate ischemia and gliosis at the microdialysis probe site and thereby improve the reliability of microdialysis measurements over the 1-10 day clinically relevant time window post-injury.

 描述(申请人提供)：脑损伤导致皮质扩散性抑制现象。在健康的大脑中，广泛性抑郁与偏头痛有关，但尚不清楚是否会导致大脑损伤。在受伤的大脑中，反复出现的弥漫性抑郁会导致继发性脑损伤，并与初次损伤后6个月死亡、植物状态或严重残疾等不良患者预后显著相关。脑损伤患者的微透析显示，扩散性抑郁症会耗尽大脑葡萄糖，反映出在去极化波通过后，对能量的突然和强烈需求，以驱动脑组织依赖于ATP的复极。通过血流输送的葡萄糖跟不上需求的步伐，脑组织就会被剥夺葡萄糖。这种葡萄糖缺乏会导致高危半暗带组织的继发性损伤，导致损伤核心的扩大。目前，由于结果的差异性，临床微透析不能用于评估弥漫性抑郁症的代谢严重程度。该项目的目的是在实验动物中开发“地塞米松增强型微透析”，作为消除微透析探头部位的缺血和胶质增生的一种方法，从而提高可靠性。 在伤后1-10天的临床相关时间窗内的微透析测量。