Optimizing Environmental Enrichment to Model Preclinical Neurorehabilitation

优化环境富集以模拟临床前神经康复

• 批准号: 10789355
• 负责人: ANTHONY E. KLINE
• 金额: $ 3.05万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10789355
• 关键词: Acceleration; Address; Administrative Supplement; Adult; Affect; Affective; Age; Amantadine; Childhood; Clinical; Cognitive; Cognitive deficits; Doctor of Philosophy; Financial Support; Funding; Goals; Grant; Hispanic; Histologic; Individual; Laboratories; Latino; Medical; Mentors; Methods; Modeling; Motor; Music; Neurosciences Research; Outcome; Pediatrics; Pharmacotherapy; Pre-Clinical Model; Rattus; Recovery; Rehabilitation therapy; Research; STEM field; Survivors; Swimming; Therapeutic; Training; Traumatic Brain Injury; Writing; Zaleplon; age group; cognitive recovery; design; environmental enrichment for laboratory animals; graduate school; improved; male; motor deficit; neurological rehabilitation; parent grant; professor; skill acquisition; success; undergraduate student; volunteer

This administrative supplement request is for an increase in funds allotted to my R01 grant (5R01NS084967) to financially support Andrew Victoria, a Latino undergraduate student currently volunteering in my laboratory, as he gains additional training in neuroscience research, which will help him become more competitive for medical/graduate school. Briefly, the goals of the parent grant were to continue to refine environmental enrichment (EE), which is a non-invasive paradigm that promotes significant cognitive recovery and histological protection after experimental traumatic brain injury (TBI) and has the potential to mimic post-TBI clinical rehabilitation. The purpose is significant because TBI affects more than 10 million individuals worldwide each year and results in long-term motor and cognitive deficits, but pharmacotherapies alone have been unsuccessful. Specifically, the parent grant consists of five specific aims that are logical and crucial extensions of our previous research. Aim 1a is designed to determine whether motor, cognitive, and affective benefits can be sustained after EE is withdrawn, and if so, for how long. Aim 1b will determine if providing “refresher rehab” after the EE-induced benefits begin to wane will stabilize or re-strengthen benefits. Aims 2abc will determine whether “bridging” delayed EE, which is initiated at 7-days after TBI, with a) amantadine {10 mg/kg/day; i.p.}, b) aqua therapy {two 90 s swim sessions}, or c) music exposure (3 h per night of New Age, Ambient, or Classical - Mozart’s sonata for two pianos, K.448) as adjunct therapies during the week after TBI will augment recovery relative to non-enriched or Rehab groups, and Aim 3 will evaluate mechanisms for the bridge plus Rehab therapies. Completion of the aims will further advance a model of neurorehabilitation that mimics the real-world while addressing questions that continue to concern physiatrists, such as how long do the rehab benefits last once discontinued and can they be maintained or improved further with supplemental rehab? Can supplemental therapies before full rehab provide a better outcome? The refined model will significantly impact and advance rehabilitation-based research. The administrative supplement will afford Mr. Victoria the opportunity to continue conducting research in a well-established TBI laboratory and expand his research and professional development skills. The project that Andrew will conduct derives from Aim 2a of the parent grant, which seeks to determine whether a bridge therapy (amantadine before the initiation of EE) is more effective than amantadine or EE alone, but differs in the age group (pediatric vs. adult) being treated. Thus, the difference from the parent grant is that here the trainee will evaluate pediatrics rats, but the project is still within the scope as the same question is being asked, and answered, and the same hypothesis and methods are included. Our request will accelerate scientific research and promote diversity in the research and medical workforce. As a Hispanic male, professor, and mentor, I am committed to Andrew’s success in achieving his long-term goal of attaining his MD/PhD as well as promoting diversity in the STEM fields.

这项行政补充要求是增加了我的R01赠款的资金增加（5R01NS084967） 为了在财务上支持安德鲁·维多利亚（Andrew Victoria），这是一名拉丁裔本科生，目前在我的实验室中自愿参加 随着他在神经科学研究中获得额外的培训，这将帮助他变得更有竞争力 医学/研究生院。简而言之，父母赠款的目标是继续完善环境 富集（EE），这是一种非侵入性范式，可促进认知恢复和 实验性创伤性脑损伤（TBI）后的组织学保护，并具有模仿TBI后的潜力 临床康复。目的是重大的，因为TBI影响了全球超过1000万个人 每年都会导致长期运动和认知缺陷，但仅药物治疗就一直存在 不成功。特别是，父母的赠款由五个特定目标组成 我们以前的研究。 AIM 1A旨在确定电动机，认知和情感利益是否可以 在撤回EE之后，要维持，如果是这样，则需要多长时间。 AIM 1B将确定是否提供“复习康复” 在EE引起的福利开始下降后，将稳定或重新强度的好处。 AIMS 2ABC将确定 是否在TBI之后的7天启动的“桥接”延迟EE，a）amantadine {10 mg/kg/day; i.p.}，b） 水疗{两个90 s游泳课}或c）音乐暴露（新时代每晚3小时，环境或古典 -Mozart的两把钢琴的奏鸣曲，K.448）作为辅助疗法，TBI将增加恢复 相对于不富裕或康复组，AIM 3将评估桥梁和康复的机制 疗法。目标的完成将进一步推进模仿现实世界的神经居住模型 在谈论继续涉及物理学家的问题的同时，例如康复需要多长时间 一旦停产，可以通过补充康复进行维护或进一步改善吗？能 充分康复前补充疗法可提供更好的结果？精制模型将显着影响 并提高基于康复的研究。行政补充剂将负担维多利亚先生 有机会继续在公认的TBI实验室进行研究，并扩大他的研究和 专业发展技能。安德鲁将进行的项目来自父母赠款的AIM 2A， 试图确定桥梁治疗（EE计划之前的amantadine）是否更有效 比单独的Amantadine或EE，但在年龄组（儿科与成人）中有所不同。那， 与父母赠款的区别在于，在这里，学员将评估儿科大鼠，但该项目仍在 询问和回答相同问题的范围，相同的假设和方法是 包括。我们的要求将加速科学研究，并促进研究和医学的多样性 劳动力。作为西班牙裔男性，教授和导师，我致力于安德鲁成功实现他的成功 获得MD/PhD并促进STEM领域的多样性的长期目标。