Role of NOS3 in the Cerebrovascular Response to TBI

描述（由申请人提供）：虽然严重创伤性脑损伤（TBI）不是通常意义上的“易感基因”疾病，但对TBI的反应是损伤、个体患者的基因型和我们提供的治疗之间的复杂相互作用。在重症监护医学中，越来越多的人强调理解个体的基因组成在应对重症疾病和损伤中的作用，以及我们用于治疗这些疾病的治疗方法。迄今为止，这项工作的大部分集中在身体对休克和脓毒症的反应上。在创伤性脑损伤领域所做的工作相对较少。在这个提议中，我们计划进行一项临床研究，利用我们在脑血管病理生理学方面的专业知识和我们在Ben Taub综合医院护理的大量TBI患者，来研究NOS 3基因多态性在脑血管对严重TBI的反应中的作用。此外，我们将为已建立的组织/数据库提供患者未使用的血液、脑脊液和脑微透析样本，以便将来对其他感兴趣的基因和转录本的研究可以利用前瞻性收集的本研究入组患者脑血管反应的功能评价。提出了以下三个具体目标：具体目标#1是研究NOS 3基因多态性在人类创伤性脑损伤的脑血管反应中的作用。具体目标#2是研究NOS 3基因多态性在脑血管系统对施用L-精氨酸的反应中的作用。具体目标#3是将未使用的血液、脑脊液和微透析样本储存在已建立的组织/数据库中，并与人口统计学/生理学/治疗和遗传数据进行编码链接，这些数据是与本提案一起收集的，用于未来可能感兴趣的其他基因和转录本的研究。

DESCRIPTION (provided by applicant): Although severe traumatic brain injury (TBI) is not a disease with "susceptibility genes" in the usual sense, the response to TBI is a complex interaction among the injury, the individual patient's genotype, and the treatment that we provide. Increasingly in critical care medicine, emphasis is being placed on understanding the role that an individual's genetic makeup plays in the response to critical illness and injury, and also in response to therapies that we use to treat these disorders. Most of this work to date has concentrated on the response of the body to shock and to sepsis. Relatively little work has been done in the area of TBI. In this proposal, we plan a clinical study, using the expertise that we have in the cerebrovascular pathophysiology of TBI and the large population of TBI patients that we care for at Ben Taub General Hospital, to examine the role of polymorphisms of the NOS3 gene in the cerebrovascular response to severe TBI. In addition, we will contribute to an established tissue/data bank unused blood, cerebrospinal fluid, and cerebral microdialysis samples from the patients so that future investigations of other genes and transcripts of interest can take advantage of the prospectively collected functional evaluation of the cerebrovascular response of the patients enrolled in this study. The following three specific aims are proposed: Specific Aim #1 is to study the role of polymorphisms of the NOS3 gene in the cerebrovascular response to human traumatic brain injury. Specific Aim #2 is to study the role of polymorphisms of the NOS3 gene in the response of cerebral vasculature to administration of L-arginine. Specific Aim #3 is to store unused blood, cerebrospinal fluid, and microdialysis samples in an established tissue/data bank with a coded link to the demographic/physiological/treatment and genetic data that is collected with this proposal for future studies of other genes and transcripts that may become of interest.