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 Aim 1a is designed to determine whether motor, cognitive, and affective benefits can be sustained after EE is withdrawn, and if so, for how long.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.

此行政补充请求是为了增加分配给我的 R01 补助金 (5R01NS084967) 的资金 为目前在我的实验室做志愿者的拉丁裔本科生安德鲁·维多利亚提供经济支持， 随着他获得神经科学研究方面的额外培训，这将帮助他变得更有竞争力 医学院/研究生院。简而言之，母公司赠款的目标是继续完善环境 丰富（EE），这是一种非侵入性范例，可促进显着的认知恢复和 实验性脑外伤 (TBI) 后的组织学保护，并有可能模仿 TBI 后的情况 临床康复。其目的意义重大，因为 TBI 影响着全球超过 1000 万人 每年都会导致长期的运动和认知缺陷，但仅靠药物治疗已 不成功。具体来说，家长补助金由五个具体目标组成，这些目标是合乎逻辑且至关重要的扩展 我们之前的研究。目标 1a 旨在确定运动、认知和情感益处是否可以 EE 撤回后是否可以持续，如果可以，持续多长时间。目标 1b 将确定是否提供“复习康复” 当EE引起的效益开始减弱后，效益将会稳定或重新加强。目标 2abc 将决定 “桥接”是否会延迟 EE（在 TBI 后 7 天开始），使用 a) 金刚烷胺 {10 mg/kg/天； i.p.}, b) 水疗{两次 90 秒的游泳课程}，或 c) 音乐接触（每晚 3 小时的新世纪音乐、氛围音乐或古典音乐） - 莫扎特的两架钢琴奏鸣曲（K.448）作为 TBI 后一周的辅助疗法将促进康复 相对于非强化组或康复组，目标 3 将评估桥梁加康复的机制 疗法。目标的完成将进一步推进模仿现实世界的神经康复模型 同时解决理疗师继续关注的问题，例如康复福利能持续多久 一旦停止，可以通过补充康复来维持或进一步改善吗？能 完全康复之前的补充疗法能提供更好的结果吗？精细化模型将显着影响 并推进基于康复的研究。行政补助金将为维多利亚先生提供 有机会继续在完善的 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源自母基金的目标 2a， 旨在确定过渡疗法（开始 EE 前使用金刚烷胺）是否更有效 与单独使用金刚烷胺或 EE 相比，但治疗年龄组（儿童与成人）有所不同。因此， 与家长资助的不同之处在于，在这里，受训者将评估儿科老鼠，但该项目仍在进行中 提出和回答相同问题的范围，以及相同的假设和方法 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。作为一名西班牙裔男性、教授和导师，我致力于帮助安德鲁成功实现他的目标 获得医学博士/博士学位以及促进 STEM 领域多样性的长期目标。