42. Prior exposure to social stress sensitizes virus-induced cytokine expression during acute Theiler’s virus infection

42. Prior exposure to social stress sensitizes virus-induced cytokine expression during acute Theiler’s virus infection

S36 Abstracts / Brain, Behavior, and Immunity 23 (2009) S25–S64 The immune response to stroke is characterized by both proinflammatory and protective...

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Abstracts / Brain, Behavior, and Immunity 23 (2009) S25–S64

The immune response to stroke is characterized by both proinflammatory and protective immune responses. One cell type that regulates immune responses in the periphery is the dendritic cell (DC). A population of DCs residing in the steady-state brain, (b) DCs, were identified using a transgenic mouse that expresses enhanced-yellow-fluorescent-protein (EYFP) under the promoter for the DC marker, CD11c (CD11c-Tg). We examined the response of bDCs to transient (40 min) middle cerebral artery occlusion (MCAO) and reperfusion using this CD11c-Tg mouse. EYFP + DCs accumulated in the ischemic infarct as soon as 24 h post-MCAOreperfusion, particularly in the border of the infarct where lymphocytes accrue. DCs and infiltrating lymphocytes were phenotyped using both immunocytochemical and FACS techniques. At 72 h post-MCAO-reperfusion, DCs in the core of the infarct displayed small, activated morphologies and mature DC markers. Conversely, few EYFP + DCs in the border region displayed mature DC markers, and these cells adopted morphologies similar to that of activated microglia. To determine the contribution of resident bDCs versus peripheral DCs in the regions of damage following MCAO-reperfusion, irradiated bone marrow chimeras were generated. Results demonstrated that DCs in the core of the infarct 72 h post-ischemia were of peripheral origin, whereas DCs observed in the border were resident bDCs. These results indicate that bDCs respond to ischemic damage and are prevalent in the ischemic border where they may interact with infiltrating lymphocytes.

41. Sympathetic nervous system activation and sterile inflammation: Impact on inflammatory proteins and vascular plasticity M. Fleshner


42. Prior exposure to social stress sensitizes virus-induced cytokine expression during acute Theiler’s virus infection M.A. Frazier a, E.G. Vichaya a, E.E. Young a, C.J. Welsh b, M.W. Meagher a

40. Combat stress injuries: Toward a psychoneuroimmunological model for research, treatment, and prevention C.R. Figley a, N. Hall b, W.P. Nash c a

Tulane University, New Orleans, United States University of South Florida, United States c Combat and Operational Stress Consultant, United States

University of Colorado-Boulder, Integrative Physiology, Center for Neuroscience, Campus Box 354, Boulder, CO 80309, United States Inflammation is a tissue process that is normally adaptive and is commonly initiated in response to pathogen challenge (PAMPs) or tissue injury (DAMPs). One of the biggest health challenges today is the damage that tissues suffer when inflammatory process are inappropriately initiated, exaggerated, or persistent. In the absence of pathological challenge, exposure to both acute intense stressors and repeated psychological stressors, triggers sterile inflammatory processes. Stressor-evoked sympathetic nervous system activation likely contributes to the initiation of systemic sterile inflammatory responses. The wellcharacterized impact of stress on inflammatory proteins may have important implications for vascular function and blood pressure regulation. New work investigating the impact of repeated psychological stressor exposure on vascular cytokines, chemokines, remodeling proteins, and blood pressure regulation will also be discussed. doi:10.1016/j.bbi.2009.06.046


Dept. of Psychology, Texas A&M University, 4235 TAMU, College Station, TX 77843-4235, United States b Department of Veterinary Integrative Biosciences, Texas A&M University, United States


Combat veterans who develop a combat stress injury report greater stress and negative health consequences than those who do not. Although an association between psychological stress and altered immune function has been shown, combat stress studies have not investigated this relationship but are predicted by an emerging theoretical model of combat stress injuries. The model suggests that under intense and prolonged combat stress four clusters of symptoms emerge and confirm the presence of a combat stress injury (CSI): traumatic stress injuries, physical fatigue injuries, grief injuries, and moral crisis injuries. The paper is the first attempt to quantify the model, drawing heavily upon the field of psychoneuroimmunology. Among other things, the paper includes a description of the role of combat stress injuries mediate the effect of CSI and the role of pro-inflammatory (IFN-y) cytokine levels, such as IL-6 (especially IL-6). These cytokines are documented to impact brain regions modulating depression, sleep dysfunction, and pain perception/reception. The authors, representing three separate disciplines, will discuss the psychoneuro, psychological, and biological markers for and implications of the model for a program of research that focuses on assessing, treating, and preventing combat stress injuries.

Social stress exacerbates both the acute and chronic phase of Theiler’s murine encephalomyelitis virus (TMEV) infection. Infection of susceptible mouse strains with TMEV results in an acute CNS infection followed by a chronic demyelinating autoimmune disease, similar to MS. Exposure to social disruption (SDR) prior to TMEV infection results in increased CNS inflammation and decreased viral clearance from brain and spinal cord. These increases in CNS inflammation and viral load are accompanied by an exacerbation of TMEV-induced sickness behaviors and motor impairment. Recent evidence suggests that these effects are partially mediated by the central release of IL-6 during the stress exposure period (Meagher et al., 2007); however, the exact mechanisms remain unknown. The present study tested the hypothesis that SDR exacerbates TMEV infection through cross-sensitization of virus-induced cytokine expression. Balb/cJ mice received intracranial infusions of either an IL-6 neutralizing antibody or its vehicle before each of six 2 h SDR sessions the week prior to infection. Results indicate that exposure to SDR before infection increases virusinduced IL-6 expression in brain and spinal cord, and produces corresponding increases in sickness behaviors and motor impairment during acute infection. Importantly, these effects are prevented by central infusion of the IL-6 neutralizing antibody during the stress exposure period. These findings suggest that SDR exacerbates acute Theiler’s virus infection through cross-sensitization of virus-induced cytokine expression. Supported by NIH/NINDS R01-NS060822.