Dissertation/Thesis Abstract

Neural regulation of inflammation and bleeding
by Czura, Christopher Jordan, Ph.D., State University of New York at Stony Brook, 2009, 141; 3401699
Abstract (Summary)

Recent advances in the field of immunology have revealed an unexpected role for the autonomic nervous system, specifically the vagus nerve, in controlling challenges to homeostasis. This work has reinforced the necessity to study disease within the context of whole-animal physiology, and has identified several approaches to develop novel therapeutic agents for inflammatory disease. While well-defined molecular responses to tissue injury can be modulated to therapeutic advantage, significant morbidity and mortality subsequent to traumatic injury remains a daunting clinical challenge. Application of physiological approaches to management of hemostasis may identify previously unrecognized pathways that can be harnessed to control hemorrhage. To this end, studies were performed to determine whether the vagus nerve controls hemostasis and homeostasis in mice and pigs. Electrical vagus nerve stimulation attenuated systemic inflammatory responses in a porcine model of septic shock, as indicated by significantly reduced circulating levels of tumor necrosis factor and inhibition of systemic coagulopathy, as well an improved mean arterial blood pressure. Vagus nerve stimulation also regulated hemostasis in a porcine model of soft tissue injury, as indicated by decreased bleeding time and total shed blood volume, and increased coagulation factor activity. In a murine model of soft tissue injury, vagus nerve regulation of hemostasis was dependent upon the α7 subunit of the nicotinic acetylcholine receptor, and pharmacological agents selective for α7 were similarly able to reduce bleeding times in mice. Together, these observations indicate that a previously unrecognized neural pathway mediated via the vagus nerve, and a molecular mechanism requiring the α7 subunit of the acetylcholine receptor, regulates hemostasis in vivo. A greater understanding of cholinergic regulation of hemorrhage may provide new opportunities to develop more effective hemostatic agents.

Indexing (document details)
Advisor: Tracey, Kevin J.
Commitee:
School: State University of New York at Stony Brook
School Location: United States -- New York
Source: DAI-B 71/04, Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Immunology
Keywords: Bleeding, Hemostasis, Inflammation, Thrombin, Vagus nerve
Publication Number: 3401699
ISBN: 9781109690446
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