A PILOT TO DETERMINE INFLUENCE OF APOLIPOPROTEIN E GENE ON OUTCOMES IN PEDIATRIC

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。神经系统（脑、脊髓和神经）的创伤性损伤在儿童中发生的频率越来越高，导致大量的死亡、疼痛、残疾和经济困难。例如，每年有超过1，000，000名儿童遭受轻度至重度脑损伤，估计有超过30，000名儿童导致永久残疾。在急诊室提供的医疗干预和后来在康复治疗“神经创伤”已被证明是只有适度的成功，导致新的研究，以解决这些问题的呼吁。基因（DNA）是构建我们身体的设计模板，近年来，我们对DNA的了解呈指数级增长，沿着的是，我们将这些基因及其蛋白质产物与疾病状态或科普伤害的能力相关联的能力。这项研究旨在证明载脂蛋白E（ApoE）基因与儿童大脑和脊髓从损伤中恢复的能力之间存在联系，ApoE的蛋白质产物促进脂肪和胆固醇在全身的运动。研究表明，ApoE对神经系统内的细胞生长和建立新的连接很重要。有3种不同形式的ApoE可以被人类遗传（ApoE 2，3和4），每种形式的功能不同。ApoE 4形式，在多达40%（平均23%）的人群中发现，与阿尔茨海默病的风险增加有关，其存在预示着成人神经创伤的损伤更严重，恢复更差。在动物中，缺乏ApoE也会导致神经系统创伤后损伤的严重程度增加，学习和记忆能力下降。到目前为止，还没有研究确定E4形式的载脂蛋白E是否会降低儿童从大脑或脊髓损伤中恢复的能力。这项研究将比较儿童如何从过去的脑或脊髓损伤中恢复，以及他们从父母那里继承了哪些形式的ApoE基因。此外，将对未来的脑/脊髓损伤儿童进行更全面的评估，以回答其他相关问题，例如：患者是男性还是女性是否有区别，他们受伤时的年龄是否重要，他们受伤的严重程度是否起作用，或者如果孩子已经进入青春期是否重要？这些研究的重要性在于我们能够根据遗传因素识别出有更严重脑损伤和残疾风险的儿童。如果可以建立这种联系，那么可以根据与这些遗传影响相关的缺陷设计治疗方案。

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 injury to the nervous system (brain, spinal cord, and nerves) occurs with increasing regularity in children causing an enormous amount of death, pain, disability and financial hardship. For example over 1,000,000 children each year sustain mild to severe brain injuries with estimates that over 30,000 result in permanent disability. Medical interventions provided in the emergency room and later in rehabilitation to treat "neurotrauma" have proven to be only moderately successful leading to a call for new research to address these issues. Knowledge of genes (DNA), the design templates on which our bodies are built, has increased exponentially in recent years and along with it our ability to associate these genes and their protein products with disease states or the ability to cope with injury. This study seeks to demonstrate that there is a link between the gene for Apolipoprotein E (ApoE), whose protein product facilitates the movement of fats and cholesterol throughout the body, and the ability of a child's brain and spinal cord to recover from injury. Research indicates that ApoE is important for cells within the nervous system to grow and make new connections. There are 3 different forms of ApoE which can be inherited by humans (ApoE2, 3, & 4) and each form varies in its ability to function. The ApoE4 form, found in as much as 40% (23% on average) of the population, has been associated with increased risk for Alzheimer's Disease and its presence predicts a more severe injury and poorer recovery from neurotrauma in adults. In animals, lack of ApoE also results in increased severity of injury after trauma to the nervous system and diminished capacity for learning and memory. To date, no research has been done to determine if having the E4 form of Apolipoprotein E diminishes the ability of children to recover from injury to their brain or spinal cord. This study will compare how children have recovered from brain or spinal cord injury in the past to which forms of the ApoE gene they have inherited from their parents. In addition, a more thorough evaluation of future brain/spinal cord injured children will be done to answer other related questions such as: does it make a difference if the patients are male or female, is their age upon injury important, does the severity of their injury play a role, or does it matter if the child has reached puberty? The importance of these studies lies in our ability to identify children at risk for more severe brain injuries and disability based on genetic factors. If this link can be established then a treatment option may be designed based on defects associated with these genetic influences.