Examining Vascular Regulation Following Acute Stroke

检查急性中风后的血管调节

• 批准号: 8848408
• 负责人: Sandra A Billinger
• 金额: $ 10.22万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-08 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8848408
• 关键词: Acute; Address; Admission activity; Aerobic Exercise; Affect; Age; Blood; Blood Vessels; Blood flow; Brain; Brain Injuries; Caliber; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cell Adhesion Molecules; Cerebrum; Chronic; Clinic; Clinical Trials; Coin; Computer software; Consent; Control Groups; Data; Data Analyses; Development; Doppler Ultrasound; Drops; Elderly; Electronics; Endothelium; Ensure; Environment; Enzyme-Linked Immunosorbent Assay; Event; Exercise; Exercise Tolerance; Faculty; Funding; Goals; Grant; Growth; Health; Hospitalization; Hospitals; Hour; Hypertension; Hypoxia; Individual; Inflammatory; Inpatients; Institutes; Interleukin-6; Intervention; Journals; K-Series Research Career Programs; Lead; Learning; Leg; Limb structure; Mediating; Mentors; Mentorship; Metabolic; Methods; Neurologic; Nitric Oxide; Operant Conditioning; Outcome; Patients; Performance; Peripheral; Peripheral Resistance; Phase; Physical activity; Physiological; Physiology; Plasma; Problem Solving; Production; Publications; Recording of previous events; Recruitment Activity; Recurrence; Regulation; Rehabilitation Research; Research; Research Personnel; Research Proposals; Resources; Role; Sampling; Scanning; Side; Staging; Stress; Stroke; Survivors; TNF gene; Techniques; Testing; Tissues; Training; Training Programs; United States; United States National Institutes of Health; Upper Extremity; Vascular Cell Adhesion Molecule-1; Vascular Diseases; Vascular System; Vasodilation; Vasodilator Agents; Walking; Wood material; Work; Writing; acute stroke; base; brachial artery; career; career development; chronic stroke; cytokine; disability; experience; femoral artery; functional outcomes; hemiparesis; improved; inflammatory marker; innovation; meetings; patient population; post stroke; programs; rehabilitation strategy; research study; response; sedentary; shear stress; skills; skills training; stroke recovery; stroke rehabilitation

DESCRIPTION (provided by applicant): The candidate for this Mentored Career Development Award has as long-term goals to: 1) increase her exposure, experience and credibility in vascular physiology as it relates to stroke; 2) obtain formal and informal training experiences that are essential to developing a long-term plan of study in rehabilitation research; and 3) execute and expand her comprehensive training program into an independent research career and submit an R01 application. The candidate's immediate goals that support her long-term goals will be to focus on: 1) obtaining a better understanding of vascular physiology (through courses and lab experiences) to understand the mechanistic vascular changes that may occur as a result of an acute stroke; 2) acquiring the essential skills to conduct experiments and data analysis for flow-mediated dilation (FMD), Doppler ultrasound and the specialized, vascular wall tracking software; 3) understanding how aerobic exercise early in stroke rehabilitation reduces vascular dysfunction; and 4) gathering results and pilot data to become an independent investigator on an R01 submission. The mentorship, training plan and environment that the candidate will have access to are robust and will ensure successful career development. The mentors for this Career Development Award have the background and experience that is complementary to the candidate's and they are committed to helping her succeed and meet her goals. Dr. Billinger's mentors have experience and a track-record of NIH funding, numerous publications and a history of mentoring junior faculty/researchers. Each mentor uniquely contributes to the candidate's scientific and career growth towards independence. Dr. Nudo, the primary mentor, will help the candidate with understanding brain physiology, the cascade of cerebral cellular events that occur after stroke, grantsmanship, improving scientific writing skills for high-impact journal submissions and NIH grants, and conducting mechanistic, hypothesis driven research. Dr. Dengel, co-mentor, will be instrumental for learning how to perform FMD techniques, using Doppler ultrasound for vascular scanning and interpreting findings using electronic vessel-wall tracking software. Dr. Dawn, co-mentor, will provide lab experiences and research discussions on vascular physiology, blood flow, and autonomic control. He will facilitate a productive learning environment between the candidate and the vascular sonographers. Dr. Wood, co-mentor, will provide lab experiences and mentorship regarding vascular regulation and benchtop techniques for identifying mechanisms related to reduced blood flow, hypoxia and vascular dysfunction. Dr. Billinger will be using the ELISA techniques in Dr. Wood's lab for identifying the pro-inflammatory in plasma. Dr Rymer, co-mentor, will ensure access to the stroke patient population and resources to conduct the experiments at the hospital (St. Luke's Brain Institute). She has been part of several clinical trials and can assist the candidate with approaches and problem-solving on recruitment, consenting, and drop-outs. Research Plan: Individuals with chronic stroke demonstrate reduced blood flow in the hemiparetic limb. A better understanding of mechanistic factors that influence vascular regulation after stroke could lead to innovative rehabilitation strategies that diminish disability and improve functional outcomes. Pro-inflammatory markers are released after stroke as a result of the brain injury. The pro-inflammatory markers enter the peripheral vascular system within 24 hours post-stroke. Cytokines (TNF-a, IL-6) and vascular adhesion molecule (VCAM-1) are pro-inflammatory markers that, when present in the vascular system, can reduce production and/or release of nitric oxide, a potent vasodilator. Nitric oxide is needed for vessel dilation to occur in order to accommodate increased blood flow during periods of exercise. Although people post-stroke demonstrate altered vascular function, pilot work suggests exercise can improve blood flow in the hemiparetic limb. The candidate will recruit individuals after an acute stroke to examine the relationship between pro-inflammatory markers and vascular function (using flow-mediated dilation). Plasma samples will be analyzed to quantitatively determine the amount of pro-inflammatory markers in the plasma. Doppler ultrasound and specialized vessel wall tracking software will be used to assess vascular function. In the most innovative aspect of the project, the candidate will also explore the role of an aerobic exercise intervention during stroke rehabilitation. The candidate believes that the exercise intervention will down-regulate the effect of pro-inflammatory markers and improve vascular regulation. The candidate plans to use the results from these experiments as pilot data for a larger clinical trial. However, before a clinical trial is undertaken, it is important and essential that one understands the role of pro-inflammatory markers and vascular function during stroke recovery.

描述（由申请人提供）：该指导职业发展奖的候选人的长期目标是：1）增加她在与中风有关的血管生理学方面的曝光，经验和可信度; 2）获得正式和非正式的培训经验，这对制定康复研究的长期学习计划至关重要;和3）执行并将她的综合培训计划扩展为独立的研究生涯，并提交R 01申请。候选人支持其长期目标的近期目标将集中于：1）更好地理解血管生理学（通过课程和实验室经验）了解急性中风可能导致的机械血管变化; 2）掌握进行血流介导的扩张（FMD），多普勒超声和专业实验和数据分析的基本技能，血管壁跟踪软件; 3）了解中风康复早期的有氧运动如何减少血管功能障碍; 4）收集结果和试点数据，成为R 01提交的独立研究者。 候选人将获得的辅导、培训计划和环境是强大的，将确保成功的职业发展。该职业发展奖的导师具有与候选人互补的背景和经验，他们致力于帮助候选人取得成功并实现目标。比林格博士的导师有经验和NIH资金的跟踪记录，许多出版物和指导初级教师/研究人员的历史。每位导师都对候选人的科学和职业发展做出了独特的贡献。 Nudo博士，主要导师，将帮助候选人了解脑生理学，中风后发生的脑细胞事件的级联，granectin，提高高影响力期刊提交和NIH赠款的科学写作技能，并进行机械，假设驱动的研究。 Dengel博士，共同导师，将有助于学习如何执行FMD技术，使用多普勒超声血管扫描和解释使用电子血管壁跟踪软件的结果。 道恩博士，共同导师，将提供实验室经验和血管生理学，血流和自主控制的研究讨论。他将促进候选人和血管超声医师之间的有效学习环境。 伍德博士，共同导师，将提供实验室经验和指导有关血管调节和台式技术，以确定有关减少血流量，缺氧和血管功能障碍的机制。比林格博士将在伍德博士的实验室使用ELISA技术来鉴定血浆中的促炎物质。 赖默博士，共同导师，将确保获得中风患者人口和资源进行实验在医院（圣卢克的大脑研究所）。她已经参加了几项临床试验，可以帮助候选人解决招募，同意和退出方面的方法和问题。 研究计划：慢性中风患者表现出偏瘫肢体血流量减少。更好地了解影响中风后血管调节的机械因素可能会导致创新的康复策略，减少残疾和改善功能结果。促炎性标记物在中风后由于脑损伤而释放。促炎标记物在中风后24小时内进入外周血管系统。细胞因子（TNF-α、IL-6）和血管粘附分子（VCAM-1）是促炎标志物，当其存在于血管系统中时，可以减少一氧化氮（一种有效的血管扩张剂）的产生和/或释放。血管扩张需要一氧化氮，以适应运动期间增加的血流量。虽然中风后的人表现出血管功能的改变，但试点工作表明，运动可以改善偏瘫肢体的血流。候选人将招募急性中风后的个体，以检查促炎标志物和血管功能之间的关系（使用流量介导的扩张）。将分析血浆样本，以定量测定血浆中促炎标志物的量。多普勒超声和专门的血管壁跟踪软件将用于评估血管功能。在该项目最具创新性的方面，候选人还将探索有氧运动干预在中风康复过程中的作用。候选人认为，运动干预将下调促炎标志物的作用，并改善血管调节。候选人计划使用这些实验的结果作为更大规模临床试验的试点数据。然而，在进行临床试验之前，了解促炎标志物和血管功能在卒中恢复期间的作用是重要和必要的。

项目成果

Does aerobic exercise and the FITT principle fit into stroke recovery?

• DOI: 10.1007/s11910-014-0519-8
• 发表时间: 2015
• 期刊: Current neurology and neuroscience reports
• 影响因子: 5.6
• 作者: Billinger SA;Boyne P;Coughenour E;Dunning K;Mattlage A
• 通讯作者: Mattlage A

Self-report sleep quality combined with sleep time variability distinguishes differences in fatigue, anxiety, and depression in individuals with multiple sclerosis: A secondary analysis.

自我报告的睡眠质量与睡眠时间的变异性可以区分多发性硬化症患者疲劳、焦虑和抑郁的差异：二次分析。

• DOI: 10.1177/2055217318815924
• 发表时间: 2018
• 期刊: Multiple sclerosis journal - experimental, translational and clinical
• 作者: Siengsukon,CatherineF;Alshehri,Mohammed;Aldughmi,Mayis
• 通讯作者: Aldughmi,Mayis

Individuals with mild MS with poor sleep quality have impaired visuospatial memory and lower perceived functional abilities.

睡眠质量差的轻度多发性硬化症患者的视觉空间记忆受损，感知功能能力较低。

• DOI: 10.1016/j.dhjo.2017.04.011
• 发表时间: 2018
• 期刊: Disability and health journal
• 影响因子: 4.5
• 作者: Siengsukon,CatherineF;Aldughmi,Mayis;Kahya,Melike;Lynch,Sharon;Bruce,Jared;Glusman,Morgan;NessNorouzinia,Abigail;Billinger,Sandra
• 通讯作者: Billinger,Sandra

Dose-Response of Aerobic Exercise on Cognition: A Community-Based, Pilot Randomized Controlled Trial.

• DOI: 10.1371/journal.pone.0131647
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Vidoni ED;Johnson DK;Morris JK;Van Sciver A;Greer CS;Billinger SA;Donnelly JE;Burns JM
• 通讯作者: Burns JM

Estimated Prestroke Peak VO2 Is Related to Circulating IGF-1 Levels During Acute Stroke.

估计中风前峰值摄氧量与急性中风期间循环 IGF-1 水平相关。

• DOI: 10.1177/1545968316656056
• 发表时间: 2017
• 期刊: Neurorehabilitation and neural repair
• 影响因子: 4.2
• 作者: Mattlage,AnnaE;Rippee,MichaelA;Abraham,MichaelG;Sandt,Janice;Billinger,SandraA
• 通讯作者: Billinger,SandraA