Neurotrophin Treatment for Pediatric Brain Injury

应聘者描述(由申请者提供)：应聘者的目标是通过与宾夕法尼亚大学和德雷克塞尔大学医学院的一群杰出的导师和咨询委员会进行培训，成为儿科创伤性脑损伤(TBI)研究领域的独立临床医生和科学家。宾夕法尼亚大学和德雷克塞尔大学的环境拥有丰富的资源和人员，因此这位初级研究员将更加熟练地掌握本研究提案中概述的实验室技能、科学写作、研究设计和实验方法。胡医生是费城儿童医院、宾夕法尼亚大学医学院的儿科重症监护内科医生，负责照顾患有创伤性脑损伤(TBI)的儿童。尽管脑外伤是导致儿童后天性残疾和死亡的头号原因，但在急性情况下只能提供支持性护理。头部受伤的儿童往往会出现慢性学习(认知)缺陷。脑损伤后，大脑似乎瞬时增加内源性分子，称为神经营养因子，如胰岛素样生长因子I(IGF-I)和神经生长因子(NGF)，其在儿童脑中表达最高，通过促进树突状细胞生长、突触效能和抑制与创伤性轴突损伤有关的钙蛋白酶而对恢复至关重要。利用临床相关的儿童闭合性脑损伤模型，本研究的目的是证明外源性应用这些营养因子可以促进树突状细胞的生长和突触效能，并抑制钙蛋白酶介导的轴突损伤，从而预防慢性认知功能障碍。这些研究与公共卫生非常相关，因为它们将为未来的研究提供理论基础，以开发新的翻译疗法，以抑制与慢性行为缺陷相关的细胞过程，并促进头部受伤儿童的大脑恢复。

DESCRIPTION (provided by applicant): The candidate's goal is to become an independent clinician-scientist in pediatric traumatic brain injury (TBI) by training with an outstanding group of mentors and an advisory committee from the University of Pennsylvania and Drexel University College of Medicine who are authorities in the field of pediatric TBI research. The environment at Penn and Drexel are rich with resources and personnel so that this junior investigator will become more facile with laboratory skills, scientific writing, research design and experimental methodology outlined in this research proposal. Dr. Huh is a pediatric critical care physician at Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, who takes care of children with traumatic brain injury (TBI). Despite the fact that TBI is the number one cause of acquired disability and death in children, only supportive care can be provided in the acute setting. Head-injured children are often left with chronic learning (cognitive) deficits. Following TBI, the brain appears to transiently increase endogenous molecules called neurotrophic factors such as Insulin-like growth factor I (IGF-I) and Nerve growth factor (NGF), whose expression is highest in the pediatric brain and important for recovery by promoting dendritic growth, synaptic efficacy, and inhibiting calpains, proteases implicated in traumatic axonal damage. Using a clinically relevant model of closed head injury in pediatric rats, the goals of this research proposal are to demonstrate that the exogenous administration of these trophic factors can enhance dendritic growth and synaptic efficacy, and inhibit calpain-mediated axonal injury to prevent chronic cognitive deficits. These studies are very relevant to public health because they will provide the rationale for future investigations for the candidate to develop novel translational therapies to inhibit cellular processes associated with chronic behavioral deficits and to enhance brain recovery in head-injured children.