Genetics and Brain Ischemia in the Critically Ill

危重病人的遗传学和脑缺血

• 批准号: 6577561
• 负责人: Mary E. Kerr
• 金额: $ 9.94万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6577561
• 关键词: brain circulation; brain injury; brain metabolism; cerebral ischemia /hypoxia; cerebrospinal fluid; clinical research; gene deletion mutation; genetic screening; genetic susceptibility; glucose transport; human mortality; human subject; human therapy evaluation; human tissue; longitudinal human study; mitochondrial DNA; nervous system disorder diagnosis; nervous system disorder therapy; neurogenetics; oxygen transport; patient oriented research; perfusion; postmortem

DESCRIPTION (provided by applicant): This K24 Midcareer Investigator application describes the investigator's dedication to patient-oriented research, her experience in mentoring young researchers, and how this award would consolidate and develop these career commitments. The clinical focus of this application is the identification of genetic factors that will maximize cerebral perfusion in the critically ill patient with brain injury. The specific aims for this study are to: 1) describe the incidence of two common mitochondrial DNA (mtDNA) deletions (4799bp and 7436 bp) found in the cerebrospinal fluid (CSF) within the acute phase following brain injury; 2) determine whether the presence of mtDNA deletions are associated with cerebral profusion and metabolism and; 3) determine whether mtDNA deletions are associated with outcomes [Glasgow Outcomes Scale (GOS) and morality]. A descriptive comparative design will be used to determine whether the presence of mtDNA deletions decreases cerebral blood flow (CBF) and metabolism and results in poorer outcomes in critically ill brain injured patients. Two currently funded clinical research projects [Methods of Predicting Delayed Cerebral lschemia in Subarahnoid Hemorrhage, and The Effect of ApoE Genotype on Outcomes in Traumatic Brain Injured Adults] will provide the foundation for the mentoring activities that will enhance and develop young investigators' clinical research skills. They will also provide patient data on the timing, severity, type, and location of insult, demographic information, CSF for analysis, CBF and ischemia data, physiologic parameters and outcome evaluation. The long-term career objective is to identify profiles of patients based on genetic variation that will allow clinicians to design individualized interventions to maximize cerebral perfusion. The focus of inter-individual variations of patients with a severe brain injury will provide the opportunity to educate and mentor junior clinical investigators in the design, implementation, evaluation and dissemination of clinical studies that will, in the long term, improve patient outcomes. The studies are designed as a combination of basic and clinical science in order to directly apply the results to clinical practice. The incorporation of an individual' s genetic profile for maximizing cerebral perfusion provides an excellent platform for training the next generation of patient-oriented critical care researchers.

描述（由申请人提供）：此K24中级研究员的申请描述了研究者对以患者为导向的研究的奉献精神，她在指导年轻研究人员方面的经验以及该奖项将如何巩固和发展这些职业承诺。该应用的临床重点是鉴定遗传因素，这些因素将使脑损伤重症患者最大化脑灌注。这项研究的具体目的是：1）描述在脑损伤后急性期内发现在脑脊髓液（CSF）中发现的两种常见线粒体DNA（mtDNA）缺失（4799bp和7436 bp）的发生率； 2）确定mtDNA缺失的存在是否与脑大量和代谢有关； 3）确定mtDNA缺失是否与结果[格拉斯哥结局量表（GOS）和道德性]相关。 描述性比较设计将用于确定MTDNA缺失的存在是否降低了脑血流（CBF）和代谢，并导致严重病重的脑损伤患者的结局较差。目前有两个资助的临床研究项目[预测亚蛛网膜下腔出血中延迟的大脑LSCHEMIA的方法，以及APOE基因型对创伤性脑损伤成年人的结果的影响]将为培训活动提供基础，以增强和发展年轻研究者的临床研究技能。他们还将提供有关侮辱性，人口统计信息，CSF的时间，严重性，类型和位置的患者数据，用于分析，CBF和缺血数据，生理参数和结果评估。长期职业目标是根据遗传变异来确定患者的特征，这将使临床医生能够设计个性化的干预措施以最大程度地提高脑灌注。严重脑损伤患者的个体间变异的重点将为教育和指导初级临床研究人员进行设计，实施，评估和传播临床研究的临床研究，从而长期改善患者结果。这些研究被设计为基础科学和临床科学的结合，以将结果直接应用于临床实践。将个体的遗传特征纳入最大化脑灌注，为训练下一代以患者为导向的重症监护研究人员提供了一个绝佳的平台。