Optimizing Environmental Enrichment to Model Preclinical Neurorehabilitation

点击翻译按钮获取中文摘要

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 Aim 1a is designed to determine whether motor, cognitive, and affective benefits can be sustained after EE is withdrawn, and if so, for how long.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