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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。神经系统(脑、脊髓和神经)的创伤性损伤在儿童中的发生率越来越高，导致大量的死亡、疼痛、残疾和经济困难。例如，每年有100多万儿童遭受轻微到严重的脑损伤，估计有30,000多人导致永久性残疾。事实证明，在急诊室和后来的康复治疗中提供的治疗“神经创伤”的医疗干预措施只取得了一定的成功，因此需要进行新的研究来解决这些问题。基因(DNA)是我们身体的设计模板，近年来我们的知识呈指数级增长，我们将这些基因及其蛋白质产物与疾病状态或应对伤害的能力联系起来的能力也随之增加。这项研究试图证明，载脂蛋白E(ApoE)的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。载脂蛋白E的蛋白质产物促进脂肪和胆固醇在全身的运动。研究表明，载脂蛋白E对于神经系统内的细胞生长和建立新的连接非常重要。人类可以遗传三种不同的载脂蛋白E形式(载脂蛋白2、载脂蛋白3和载脂蛋白4)，每种形式的功能都不同。在多达40%(平均23%)的人群中发现了ApoE4形式，这种形式与阿尔茨海默病风险增加有关，它的存在预示着成年人的损伤更严重，神经创伤的恢复更差。在动物中，缺乏载脂蛋白E还会导致神经系统创伤后损伤的严重性增加，学习和记忆能力减弱。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过去如何从脑或脊髓损伤中恢复过来，以及他们从父母那里继承了哪些形式的ApoE基因。此外，还将对未来的脑/脊髓损伤儿童进行更彻底的评估，以回答其他相关问题，如：患者是男性还是女性有区别吗？他们受伤时的年龄重要吗？他们受伤的严重程度起作用吗？或者孩子是否已经进入青春期？这些研究的重要性在于我们有能力基于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来设计治疗选项。

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.