Role of NOS3 in the Cerebrovascular Response to TBI

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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.