Voluntary Exercise Therapy after Traumatic Brain Injury

脑外伤后的自愿运动治疗

• 批准号: 6922334
• 负责人: GRACE S. GRIESBACH
• 金额: $ 21.4万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6922334
• 关键词: behavior test; brain derived neurotrophic factor; brain injury; exercise; gene expression; hippocampus; immunocytochemistry; laboratory rat; learning; memory; nervous system disorder therapy; nonhuman therapy evaluation; polymerase chain reaction; therapy design /development; trauma

DESCRIPTION (provided by applicant): Traumatic brain injury (TBI) is one of the leading causes of disability in our society. Unfortunately, there is no specific treatment for TBI. Brain derived neurotrohic factor (BDNF) is a key player in neuronal survival, growth and plasticity. These qualities provide it with therapeutic capabilities. However, BDNF-based treatments have been limited by delivery problems. I propose to endogenously upregulate BDNF and associated molecular systems with exercise following TBI. The concept of endogenously upregulating molecules important in synaptic plasticity after TBI is an uncharted area of research that could have an impact on rehabilitative startegies. However, during the first days to weeks following TBI, the brain is in a state of energy crisis that may compromise the reactivity of molecular systems to physiological stimulation as a result of exercise. I would like to determine to what degree BDNF and associated molecular systems respond to TBI and subsequent voluntary exercise. In order to address this topic the following specific aims are proposed to: Specific Aim 1: Determine if injury-induced changes in BDNF and associated proteins involved with synaptic plasticity are time and severity dependent. Within this aim I will determine the effects of a lateral fluid percussion injury (FPI) on hipppocampal and cortical BDNF (and associated molecules) at postinjury times that are pertinent to the recovery and rehabilitative period. Specific Aim 2: Determine the post-traumatic time window in which exercise can produce an endogenous up-regulation of BDNF (and its associated molecular systems). Within this aim I will determine the period of time following injury when voluntary exercise does not result in an up-regulation of BDNF and determine if this time window is injury-severity dependent. Specific Aim 3: Determine the short and long-term effects of exercise on cognitive outcome and determine if any exercise-induced improvement is dependent on BDNF. The Morris Water Maze (MWM) will be used to assess learning acquisition and memory performance. In order to address these specific aims, I will utilize the lateral fluid-percussion injury model in rats and voluntary running wheel exposure. Protein, gene, histological and behavioral studies will be conducted.

描述（由申请人提供）：创伤性脑损伤（TBI）是我们社会残疾的主要原因之一。不幸的是，TBI 没有具体的治疗方法。脑源性神经营养因子（BDNF）在神经元存活、生长和可塑性中发挥着关键作用。这些品质为其提供了治疗能力。然而，基于 BDNF 的治疗受到递送问题的限制。我建议通过 TBI 后的锻炼来内源性上调 BDNF 和相关分子系统。 TBI 后突触可塑性中重要的内源性上调分子的概念是一个未知的研究领域，可能会对康复策略产生影响。然而，在 TBI 后的最初几天到几周内，大脑处于能量危机状态，可能会损害分子系统对运动引起的生理刺激的反应性。我想确定 BDNF 和相关分子系统对 TBI 和随后的自愿锻炼的反应程度。为了解决这一主题，提出以下具体目标： 具体目标 1：确定损伤引起的 BDNF 和与突触可塑性相关的蛋白的变化是否与时间和严重程度相关。在这个目标中，我将确定横向液体冲击损伤 (FPI) 在与恢复和康复期相关的损伤后时间对海马和皮质 BDNF（以及相关分子）的影响。 具体目标 2：确定运动可以产生 BDNF（及其相关分子系统）内源性上调的创伤后时间窗口。在此目标下，我将确定受伤后自愿锻炼不会导致 BDNF 上调的时间段，并确定该时间窗口是否与受伤严重程度相关。 具体目标 3：确定运动对认知结果的短期和长期影响，并确定运动引起的改善是否依赖于 BDNF。莫里斯水迷宫 (MWM) 将用于评估学习习得和记忆表现。为了实现这些具体目标，我将利用大鼠的横向流体冲击损伤模型和自愿跑轮暴露。将进行蛋白质、基因、组织学和行为研究。