权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Nitrite based neuroprotection after cardiac arrest

心脏骤停后基于亚硝酸盐的神经保护

基本信息

批准号：
8299091
负责人：
Cameron Dezfulian
金额：
$ 17.38万
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：
2010
资助国家：
美国
起止时间：
2010-09-15 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8299091
关键词：
Adult Advisory Committees Affect Apoptosis Apoptotic Brain Brain Injuries Brain Ischemia Cardiac Caring Cessation of life Childhood Clinical Critical Care Cyclic GMP Development Development Plans Dose Funding Generations Grant Grant Review Hares Heart Arrest Heart failure Hippocampus (Brain)Injury Institutes Instruction Intensive Care Units Ischemia Journals K-Series Research Career Programs Knock-out Knowledge Laboratories Mediating Mentors Mentorship Mitochondria Modeling Nervous System Trauma Neurologic Neurons Neurosciences Nitric Oxide Nitric Oxide Synthase Nitrites Oxidation-Reduction Oxidative Stress Pathway interactions Patients Physicians Physiology Production Reactive Nitrogen Species Reactive Oxygen Species Relative (related person)Reperfusion Injury Reperfusion Therapy Reporting Research Research Support Resuscitation Role S-Nitrosothiols Scientist Senior Scientist Series Signal Pathway Signal Transduction Stem cells Survivors Testing Therapeutic Time Training Translations United States National Institutes of Health Universities Wages Work Writing base career development caspase-3 clinically relevant defined contribution design improved insight mitochondrial dysfunction mortality mouse model natural hypothermia neuroprotection novel prevent programs protein kinase C-delta public health relevance research study responsible research conduct symposium

项目摘要

DESCRIPTION (provided by applicant): Dr. Dezfulian is an adult and pediatric critical care physician acutely aware of the paucity of post-resuscitation therapies for the cardiac arrest survivors he cares for. This career development award supplements his research background with senior mentorship and lab-based and didactic training in neurosciences and redox signaling. The research plan is based on preliminary observations which support the hypothesis that nitrite-mediated neuroprotection after cardiac arrest occurs through nitric oxide (NO) and S-nitrosothiol (S-NO)-based signaling that prevents subsequent neuronal death by targeting delta protein kinase C and mitochondria. This hypothesis will be tested along three aims: (1) to define the optimal nitrite dose and timing and quantify the relative contributions of NO- and S-NO based signaling in neuroprotection, (2) to test whether nitrite-mediated neuroprotection results from nitrosylation and inactivation of delta protein kinase C (-PKC), and (3) to test whether nitrite-mediated NO and S-NO production affects mitochondrial function and prevents apoptosis. Dr. Dezfulian will undertake a career development plan consisting of: 1. Experimental research, laboratory instruction, journal clubs and scientific review and development by his mentors and colleagues. 2. Coursework through the University of Miami graduate program. 3. Intramural seminars and national conferences and symposia. 4. Training in the responsible conduct of research. 5. Guidance by a scientific advisory committee consisting of two senior MDs and two PhDs. 6. Grant writing, grant review and development of a transition plan aimed at independence. Dr. Dezfulian's neuroscience mentorship will primarily come from Dr. Miguel Perez-Pinzon, CVDRC director. Dr. Perez-Pinzon is an accomplished NIH-funded neuroscientist who studies mechanisms of neuroprotection and mitochondrial dysfunction after brain ischemia. Dr. Dezfulian will be co-mentored by Dr. Joshua Hare, Director of the Interdisciplinary Stem Cell Institute (ISCI). Dr. Hare is NIH-funded to investigate oxidative stress in heart failure, has a long track record of research in nitroso-redox signaling, and will provide guidance regarding key mechanistic pathways believed to underlie nitrite mediated neuroprotection. This mentorship team will guide Dr. Dezfulian's career development as he executes the research aims of this application and transitions to independence as a clinician scientist. PUBLIC HEALTH RELEVANCE: This career development awards provides Dr. Cameron Dezfulian, an intensive care unit physician, with salary and research support to pursue a career development plan aimed at making him an independent clinician scientist studying ways to reduce brain injury after cardiac arrest. Dr. Dezfulian will be mentored by two senior scientists at the University of Miami and conduct research aimed at discovering new ways to signal protection in brain after cardiac arrest to prevent the brain injury that normally results.

描述（由申请人提供）：Dezfulian博士是一名成人和儿童重症监护医生，他敏锐地意识到他所照顾的心脏骤停幸存者缺乏复苏后治疗。这个职业发展奖补充了他的研究背景，包括神经科学和氧化还原信号的高级导师和实验室培训。该研究计划基于初步观察，这些观察支持以下假设：心脏骤停后亚硝酸盐介导的神经保护作用通过一氧化氮（NO）和S-亚硝基硫醇（S-NO）信号传导发生，该信号传导通过靶向δ蛋白激酶C和线粒体防止随后的神经元死亡。将沿着沿着三个目标检验这一假设：（1）确定最佳亚硝酸盐剂量和时间，并量化基于NO和S-NO的信号传导在神经保护中的相对贡献，（2）测试亚硝酸盐介导的神经保护是否由δ蛋白激酶C（-PKC）的亚硝基化和失活引起，以及（3）检测亚硝酸盐介导的NO和S-NO的产生是否影响线粒体功能并阻止细胞凋亡。Dezfulian博士将进行职业发展计划，包括：1。实验研究，实验室教学，期刊俱乐部和科学审查和发展，他的导师和同事。2.通过迈阿密大学研究生课程的课程作业。3.校内研讨会和全国会议及专题讨论会。4.培训负责任地开展研究。5.由两名高级医学博士和两名博士组成的科学咨询委员会提供指导。6.编写赠款、审查赠款和制定旨在实现独立的过渡计划。Dezfulian博士的神经科学导师将主要来自CVDRC主任Miguel Perez-Pinzon博士。Perez-Pinzon博士是一位有成就的NIH资助的神经科学家，研究脑缺血后神经保护和线粒体功能障碍的机制。Dezfulian博士将由跨学科干细胞研究所（ISCI）主任约书亚黑尔博士共同指导。Hare博士是NIH资助的研究心力衰竭中的氧化应激，在亚硝基氧化还原信号传导方面有着长期的研究记录，并将提供有关亚硝酸盐介导的神经保护的关键机制途径的指导。这个导师团队将指导Dezfulian博士的职业发展，因为他执行本申请的研究目标，并过渡到独立的临床科学家。公共卫生相关性：这个职业发展奖为重症监护室医生卡梅隆德兹富利安博士提供工资和研究支持，以追求职业发展计划，旨在使他成为一名独立的临床科学家，研究如何减少心脏骤停后的脑损伤。Dezfulian博士将由迈阿密大学的两名资深科学家指导，并进行旨在发现心脏骤停后大脑保护信号的新方法的研究，以防止通常导致的脑损伤。