Date of Completion

1-11-2016

Embargo Period

1-5-2016

Keywords

Microglia, Aging, Ischemic Stroke, Neuroinflammation, CD200, CD200R1, CD8 T cells, Monocytes, Immune Surveillance, Immune Inhibitory Receptors

Major Advisor

Louise McCullough, M.D., Ph.D.

Associate Advisor

Stefan Brocke, M.D., Ph.D.

Associate Advisor

Stephen J. Crocker, Ph.D.

Associate Advisor

Betty A. Eipper, Ph.D.

Associate Advisor

Lynn Puddington, Ph.D.

Field of Study

Biomedical Science

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

The work presented herein details our efforts at characterizing and understanding the mechanisms that govern microglia homeostasis and activation in the central nervous system (CNS). These studies have focused on the microglial response to aging and ischemic stroke, highlighting the importance of neuro-immune interactions and inflammatory signaling in the brain (Chapters 1 and 2). We begin with our investigations into microglial activity following ischemic brain injury and how these responses differ from that of other bone marrow-derived monocyte populations (Chapter 3). Then we define the role of the CD200-CD200R1 immuno-inhibitory signaling axis in ischemic stroke (Chapter 4), highlighting the importance of neuronal-glial interactions in maintaining immune privilege and attenuating post-stroke inflammation. Lastly, our work on the effects of aging on microglia function (Chapter 5) and immune surveillance (Chapter 6) in the CNS furthers our understanding of microglia senescence and the phenomenon of ‘inflamm-aging’.

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