Role of the Beta-2 Adrenergic Receptor in Controlling Inflammatory Dynamics After Ischemic Stroke
Abstract/Contents
- Abstract
- Ischemic stroke is one of the leading causes of death and disability around the world. Stroke triggers inflammation in the brain, which plays a critical role in the eventual outcome of the infarct. This neuroinflammation is a dynamic process, involving microglia (the brain resident macrophages) in addition to several peripheral immune cells subsets that enter the brain from the bloodstream after stroke. Microglia and the monocyte-lineage cells that localize to the brain post- stroke highly express the beta-2 adrenergic receptor (β2-AR). Although studies have demonstrated that β2-AR signaling alters the activity of immune cells after stroke, the specifics of this modulation remain unclear. Using a mouse model of stroke, we examined the effects of stimulating or blocking this receptor with β2- AR affecting drugs on brain inflammation and infarct outcome. In addition, in order to better characterize the role of the β2-AR specifically for the microglia and invading immune cells, we created mice that had the receptor knocked out selectively in Cx3Cr1 expressing cells. Our experiments demonstrated that the stimulation of β2-AR on microglia and other invading immune cells decreased neuroinflammation by decreasing immune cell morphologic activation, rate of proliferation, and expression of pro-inflammatory cytokines. This limited inflammation resulted in an increased stroke size. In contrast, β2-AR blockade increased the expression of pro-inflammatory cytokines and increased the overall reactivity of immune cells in the stroke region. Interestingly, however, we also demonstrated that a certain degree of β2-AR activity helps spur cell proliferation. These findings elucidate some of the specific effects of β2-AR activity after stroke, allowing us to better understand the neuroinflammatory process of stroke and to identify new potential therapeutic techniques.
Description
| Type of resource | text |
|---|---|
| Date created | May 2018 |
Creators/Contributors
| Author | Meyer, Scott Thomas |
|---|---|
| Degree granting institution | Stanford University, Department of Bioengineering |
| Primary advisor | Buckwalter, Marion |
| Advisor | Covert, Markus |
Subjects
| Subject | bioengineering |
|---|---|
| Subject | neuroscience |
| Subject | neuroinflammation |
| Subject | stroke |
| Subject | post-stroke |
| Subject | adrenergic signaling |
| Subject | beta-2 adrenergic receptor |
| Genre | Thesis |
Bibliographic information
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- Use and reproduction
- User agrees that, where applicable, content will not be used to identify or to otherwise infringe the privacy or confidentiality rights of individuals. Content distributed via the Stanford Digital Repository may be subject to additional license and use restrictions applied by the depositor.
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Preferred citation
- Preferred Citation
- Meyer, Scott Thomas. (2018). Role of the Beta-2 Adrenergic Receptor in Controlling Inflammatory Dynamics After Ischemic Stroke. Stanford Digital Repository. Available at: https://purl.stanford.edu/fs868vz9310
Collection
Undergraduate Theses, School of Engineering
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- Contact
- smeyer18@alumni.stanford.edu
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