RESTORATION OF PLASTICITY AFTER PEDIATRIC TRAUMATIC BRAIN INJURY

小儿脑外伤后可塑性的恢复

• 批准号: 8171118
• 负责人: CHRISTOPHER C GIZA
• 金额: $ 0.3万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171118
• 关键词: Acute; Adolescent; Adult; Age; Behavioral; Biomechanics; Brain; Cause of Death; Child; Childhood; Chronic; Cognitive; Cognitive deficits; Computer Retrieval of Information on Scientific Projects Database; Development; Environment; Experimental Models; Functional disorder; Funding; Glutamates; Grant; Injury; Institution; Measures; Molecular Profiling; N-Methyl-D-Aspartate Receptors; Neuraxis; Neuronal Plasticity; Neurotransmitters; Pediatric Brain Injury; Problem behavior; Research; Research Personnel; Resources; Source; Structure; System; Testing; Therapeutic; Time; Traumatic Brain Injury; United States National Institutes of Health; design; disability; neurotransmission; patient population; relating to nervous system; response; restoration

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Traumatic brain injury (TBI) is the single most important cause of death and disability in children and adolescents, yet relatively little is known about the underlying mechanisms that distinguish pediatric brain injury from that in adults. It is understood the traumatic biomechanical injury to the immature brain can manifest as chronic cognitive and behavioral problems with a loss of developmental potential. Plasticity is defined as a mechanism by which the brain modifies cellular and network structure and function to respond to changes in the environment. There is increasing evidence that pediatric TBI can result in impaired plasticity and alterations in neurotransmission. Glutamate represents the major excitatory neurotransmitter in the central nervous system and is intimately involved in the acute pathophysiology of TBI, but also is critical for normal development and for neural plasticity. This application proposes to investigate the glutamatergic response to TBI in the immature brain, in particular, that which involves the N-methyl-D-aspartate (NMDA) receptor. The central hypothesis of this proposal is that dysfunction at the NMDA receptor underlies the loss of plasticity seen following developmental TBI, and that this perturbation can be measured molecularly (Specific Aims 1 and 2), electrophysiologically (Specific Aim 3) and cognitively (Specific Aim 4), using a well-characterized experimental model of pediatric TBI. By determining the post-injury time course of changes in this important neurotransmitter system, it will be possible to identify the window of impaired neural responsiveness at the NMDA receptor. Proper identification of this time period will then direct the final aim (Specific Aim 5) of this application, which is to utilize pharmacological agents that augment NMDA receptor neurotransmission to normalize the molecular profile of the developing brain and to alleviate behavioral and cognitive deficits. This proposal provides a unique opportunity to rigorously test an age-specific therapeutic strategy that is designed to be beneficial for the patient population most vulnerable to TBI, children.

这个子项目是众多研究子项目之一