Glucocorticoids increase CNS inflammation, worsening acute neurological injury
Abstract/Contents
- Abstract
- Glucocorticoids (GCs) are stress hormones that are well-known for their potent and pleiotropic anti-inflammatory effects. In the injured CNS, their anti-inflammatory properties could be particularly beneficial due to the often detrimental effects of excessive inflammation in the brain. In more recent years, however, it has become clear that GCs do not always decrease inflammation and can even augment aspects of the immune response. The research presented in this doctoral dissertation describes the impact of this increased inflammatory response in the CNS using animal models of excitotoxicity and hypoxia/ischemia. Specifically, both exogenous GC treatments and the endogenously released GCs post-injury were found to increase immune cell activation (both in phenotype and in p65 nuclear translocation) in both rat and mouse models of excitotoxic hippocampal neuron death and in a mouse MCAO stroke model. These increased inflammatory responses are likely to be mediated by an unexpected GC-suppression of several anti-inflammatory cytokines including CX3CL1 and CD22 and failure of GCs to activate some of their normal anti-inflammatory targets like IkBa, IL-1ra, and MKP-1. Furthermore, these GC-augmented inflammatory responses are necessary for GCs to make more neurons die from either of these injuries. Taken together, this work demonstrates that cellular inflammation is not kept in check by GCs in the forebrain; instead, GCs worsen hippocampal and cortical neuron death, at least in part, by increasing the neurotoxicity of CNS inflammation.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2011 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Sorrells, Shawn Fletcher |
|---|---|
| Associated with | Stanford University, Department of Biology. |
| Primary advisor | Sapolsky, Robert M |
| Thesis advisor | Sapolsky, Robert M |
| Thesis advisor | Barres, Ben |
| Thesis advisor | Dhabhar, Firdaus (Firdaus S.) |
| Thesis advisor | Wyss-Coray, Anton |
| Advisor | Barres, Ben |
| Advisor | Dhabhar, Firdaus (Firdaus S.) |
| Advisor | Wyss-Coray, Anton |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Shawn Fletcher Sorrells. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Ph.D. Stanford University 2011 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Shawn Fletcher Sorrells
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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