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Effects of the sigma-1 receptor agonist 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)-piperazine dihydro-chloride on inflammation after stroke.

Authors: Ruscher, K  Inacio, AR  Valind, K  Rowshan Ravan, A  Kuric, E  Wieloch, T 
Citation: Ruscher K, etal., PLoS One. 2012;7(9):e45118. doi: 10.1371/journal.pone.0045118. Epub 2012 Sep 18.
Pubmed: (View Article at PubMed) PMID:23028794
DOI: Full-text: DOI:10.1371/journal.pone.0045118

Activation of the sigma-1 receptor (Sig-1R) improves functional recovery in models of experimental stroke and is known to modulate microglia function. The present study was conducted to investigate if Sig-1R activation after experimental stroke affects mediators of the inflammatory response in the ischemic hemisphere. Male Wistar rats were subjected to transient occlusion of the middle cerebral artery (MCAO) and injected with the specific Sig-1R agonist 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride (SA4503) or saline for 5 days starting on day 2 after MCAO. Treatment did not affect the increased levels of the pro-inflammatory cytokines interleukin 1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), interleukin 4 (IL-4), interleukin 5 (IL-5), and interleukin 13 (IL-13) in the infarct core and peri-infarct area after MCAO. In addition, treatment with SA4503 did not affect elevated levels of nitrite, TNF-alpha and IL-1beta observed in primary cultures of microglia exposed to combined Hypoxia/Aglycemia, while the unspecific sigma receptor ligand 1,3-di-o-tolylguanidine (DTG) significantly decreased the production of nitrite and levels of TNF-alpha. Analysis of the ischemic hemisphere also revealed increased levels of ionized calcium binding adaptor molecule 1 (Iba1) levels in the infarct core of SA4503 treated animals. However, no difference in Iba1 immunoreactivity was detected in the infarct core. Also, levels of the proliferation marker proliferating cell nuclear antigen (PCNA) and OX-42 were not increased in the infarct core in rats treated with SA4503. Together, our results suggest that sigma-1 receptor activation affects Iba1 expression in microglia/macrophages of the ischemic hemisphere after experimental stroke but does not affect post-stroke inflammatory mediators.


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CRRD Object Information
CRRD ID: 7204480
Created: 2012-12-19
Species: All species
Last Modified: 2012-12-19
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.