Restoration of Homeostasis After Brain Trauma

脑外伤后体内平衡的恢复

基本信息

批准号：
7623489
负责人：
Fernando Gomez-Pinilla
金额：
$ 34.57万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-08-15 至 2010-08-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7623489
关键词：
Abbreviations Affect Aptitude Biological Brain Brain-Derived Neurotrophic Factor CREB1 gene Calcium/calmodulin-dependent protein kinase Calmodulin Cells Cognition Cognitive Cyclic AMP-Responsive DNA-Binding Protein Environment Enzyme-Linked Immunosorbent Assay Enzymes Equilibrium Event Exercise Fostering Free Radical Formation Future Homeostasis Individual Intervention Learning Memory Molecular Neurons Neurophysiology - biologic function Outcome Outcome Study Oxidative Stress Oxygen Patients Phosphotransferases Physical activity Procedures Process Production Recovery of Function Research Personnel Role Synapsin I Synaptic Transmission Synaptic plasticity System Therapeutic Traumatic Brain Injury Up-Regulation Vitamin E antioxidant therapy base calmodulin-dependent protein kinase II cognitive function coping fluid percussion injury functional restoration improved morris water maze neuronal excitability neurotrophic factor programs restoration synaptic function

项目摘要

DESCRIPTION (provided by applicant): Traumatic brain injury (TBI) is associated with a long-lasting decrement in the capacity of the brain to cope with future insults, and often with a reduced ability of individuals to maintain higher cognitive and intellectual function. It is likely that the capacity of the brain to remain functional following TBI depends upon a suitable environment for plasticity and the ability of cells to maintain synaptic transmission. In particular, oxidative stress (OS) as a primary event in the pathobiology of TBI has the power to deteriorate synaptic plasticity. This would compromise the capacity of cells to process, transmit, and store information, and ultimately disrupt higher order functions such as learning and memory. We propose studies to evaluate the hypothesis that OS and synaptic function are interrelated events such that a proper balance in free radical formation can aid synaptic plasticity and cognitive function after TBI. Brain-derived neurotrophic factor (BDNF) has a critical action on synaptic function underlying learning and memory. Based on our new findings that OS affects BDNF production and function, we propose studies to overcome dysfunctional synaptic plasticity after TBI under homeostatic conditions, by maintaining a suitable balance between OS and BDNF. Physical activity is an intrinsic component during the management of TBI patients, and is becoming commonly used therapeutically to promote functional restoration following TBI. Encouraged by our findings that physical activity reduces free radical formation and induces BDNF in the brain, we propose that exercise can be employed to improve functional recovery after TBI. We would like to evaluate the capacity of exercise to create a suitable environment for plasticity that can boost functional restoration following TBI. To date most intervention procedures for TBI have been based on adding exogenous substances into the brain ignoring the intrinsic capacity of the brain for plasticity. A positive outcome of these studies would open a new line of therapeutic treatments for TBI patients by endogenous up-regulation of neurotrophins.

描述（由申请人提供）：创伤性脑损伤（TBI）与大脑能够应对未来侮辱的能力的长期降低有关，并且通常与个人保持较高的认知和智力功能的能力降低。在TBI之后，大脑保持功能可能取决于适合可塑性的环境以及细胞维持突触传播的能力。特别是，氧化应激（OS）作为TBI病理生物学中的主要事件具有恶化的突触可塑性。这将损害细胞处理，传输和存储信息的能力，并最终破坏高阶功能，例如学习和记忆。我们建议的研究评估了OS和突触功能是相互关联的事件的假设，以使自由基形成的适当平衡可以帮助TBI后的突触可塑性和认知功能。脑衍生的神经营养因子（BDNF）对学习和记忆的突触功能具有关键作用。基于我们的新发现，即OS影响BDNF的产生和功能，我们提出了研究在稳态条件下TBI后克服功能失调的突触可塑性，通过保持OS和BDNF之间的适当平衡。体育活动是TBI患者治疗过程中的一种内在组成部分，并且正常在治疗上用于促进TBI后的功能恢复。在我们的发现的鼓励下，身体活动减少了自由基的形成并引起大脑中的BDNF，我们建议可以采用运动来改善TBI后的功能恢复。我们想评估锻炼能力，以创造适合可塑性的环境，以促进TBI之后的功能恢复。迄今为止，TBI的大多数干预程序都是基于将外源物质添加到大脑中，忽略了大脑可塑性的内在能力。这些研究的积极结果将通过内源性上调神经营养蛋白为TBI患者开辟新的治疗方法。