| Anti-Inflammatory Efficacy of Dexamethasone and Nrf2 Activators in the CNS Using Brain Slices as a Model of Acute Injury. | |
| | |
MedLine Citation:
|
PMID: 22249489 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Limiting excessive production of inflammatory mediators is an effective therapeutic strategy for many diseases. It's also a promising remedy for neurodegenerative diseases and central nervous system (CNS) injuries. Glucocorticoids are valuable anti-inflammatory agents, but their use is constrained by adverse side-effects. Activators of NF-E2-related factor-2 (Nrf2) signaling represent an attractive anti-inflammatory alternative. In this study, dexamethasone, a synthetic glucocorticoid, and several molecular activators of Nrf2 were evaluated for efficacy in slices of cerebral cortex derived from adult SJL/J mice. Cortical explants increased expression of IL-1β and TNF-α mRNAs in culture within 5 h of sectioning. This expression was inhibited with dexamethasone in the explant medium or injected systemically in mice before sectioning. Semi-synthetic triterpenoid (SST) derivatives, potent activators of the Nrf2 pathway, demonstrated fast-acting anti-inflammatory activity in microglia cultures, but not in the cortical slice system. Quercetin, luteolin, and dimethyl fumarate were also evaluated as molecular activators of Nrf2. While expression of inflammatory mediators in microglia cultures was inhibited, these compounds did not demonstrate anti-inflammatory efficacy in cortical slices. In conclusion, brain slices were amenable to pharmacological modification as demonstrated by anti-inflammatory activity with dexamethasone. The utilization of Nrf2 activators to limit inflammatory mediators within the CNS requires further investigation. Inactivity in CNS tissue, however, suggests their safe use without neurological side-effects in treating non-CNS disorders. Short-term CNS explants may provide a more accurate model of in vivo conditions than microglia cultures since the complex tissue microenvironment is maintained. |
| | |
Authors:
|
David J Graber; William F Hickey; Elijah W Stommel; Brent T Harris |
Related Documents
:
|
6840799 - Inhibition of phagocytosis by erythrocyte membrane sialoglycoprotein on target liposomes. 20587739 - Technical advance: caspase-1 activation and il-1β release correlate with the degree of... 19647209 - Immunomodulatory activity of toxicodendron pubescens in experimental models. 15949909 - Sphingomyelinase mediates macrophage activation by titanium particles independent of ph... 21903389 - A compound isolated from schisandra chinensis induces apoptosis. 1281199 - Different populations of macrophages use either the vitronectin receptor or the phospha... 22163099 - Grb2-associated binding (gab) proteins in hematopoietic and immune cell biology. 19028849 - Board-invited review: porcine mucosal immunity of the gastrointestinal tract. 15625539 - Cytokines and cytotoxic pathways in engraftment resistance to purified allogeneic hemat... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-1-17 |
Journal Detail:
|
Title: Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology Volume: - ISSN: 1557-1904 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
|
Created Date: 2012-1-17 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101256586 Medline TA: J Neuroimmune Pharmacol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Department of Pathology, Dartmouth Medical School, Lebanon, NH, 03756, USA, David.J.Graber@Dartmouth.Edu. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Use of toe clips as a nonlethal index of mercury accumulation and maternal transfer in amphibians.
Next Document: Sleep-Disordered Breathing in Neurodegenerative Diseases.