Date of Award

Spring 1-1-2012

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Psychology & Neuroscience

First Advisor

Daniel S. Barth

Second Advisor

Joanna Arch

Third Advisor

Heidi Day

Fourth Advisor

Monika Fleshner

Fifth Advisor

Theresa Hernandez

Abstract

Traumatic brain injury (TBI) is a rising public health concern, with approximately 1.7 million people in the United States alone sustaining a TBI each year (Vaishnavi et al., 2009; Faul, 2010). In addition to the physical, cognitive and behavioral impairments, the long-term consequences of TBI include increased risk of neuropsychiatric disorders, and anxiety disorders are among the most prevalent (Rao and Lyketsos, 2000; Moore et al., 2006; Vaishnavi et al., 2009). In spite of increasing evidence that anxiety disorders are elevated following TBI, very little is known about the etiology of post-traumatic anxiety. Chronic neuroinflammation is now thought to contribute to the development of post-traumatic anxiety, the primary injury initiates complex cascades that can lead to secondary injury and worsened functional outcomes. These secondary cascades may contribute to the dysfunction of brain regions and neurotransmitter systems associated with anxiety following TBI. New evidence supports this hypothesis, including peripheral elevations of proinflammatory cytokines in patients with post-traumatic stress disorder (PTSD) and panic disorder (Spivak et al., 1997; Tucker et al., 2004; von Kanel et al., 2007; Hoge et al., 2009) and anxiety-like behavior (Connor et al., 1998; Cragnolini et al., 2006; Sokolova et al., 2007; Zubareva and Klimenko, 2009) when these cytokines are administered in rats. The goal of this thesis is to better understand the role of neuroinflammation in post-traumatic anxiety. The development of post-traumatic anxiety involves a number of complex molecular, cellular, neurochemical and physiological changes, and better understanding of these processes will be needed for successful treatment strategies in this population.

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