Sigma-1 receptor ligand PRE-084 reduced infarct volume, neurological deficits, pro-inflammatory cytokines and enhanced anti-inflammatory cytokines after embolic stroke in rats.

Abstract

Sigma receptor agonists have been found to provide potent neuroprotection in rats and mice. This neuroprotection is thought to be mediated through anti-excitotoxic mechanisms. Neuroprotective and immune modulatory effects of sigma ligands have not been investigated in embolic stroke. In the present study, rats were subjected to embolic stroke or sham stroke and were treated with the sigma-1 receptor agonist PRE-084 (5mg/kg i.p.) or saline vehicle 3 and 24h after stroke. Infarct volume and behavioural tests were conducted, and cytokine levels (ILs-1α and β, IL-2, IL-4, IL-6, IL-10, GM-CSF and TNF-α) were determined in ischemic and non-ischemic cortices. Axonal damage was determined using the pNF-H ELISA assay. Treatment with PRE-084 afforded neuroprotection following embolic stroke as evidenced by significantly reduced infarct volume and improved behavioural outcome. Remarkably, treatment with PRE-084 reduced levels of pro-inflammatory cytokines and enhanced anti-inflammatory cytokines. Levels of pNF-H were lower in rats treated with PRE-084 suggesting reduced axonal damage but this finding did not reach statistical significance. The findings of the present study suggest that part of the neuroprotective effects of sigma-1 receptor agonists may be mediated through a dual effect on cytokine release following stroke.

• Authors: Mohammad Allahtavakoli, Bevyn Jarrott
• Journal: Brain research bulletin (Brain Res Bull) Vol. 85 Issue 3-4 Pg. 219-24 (May 30 2011) ISSN: 1873-2747 [Electronic] United States
• PMID: 21453760 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Cytokines
• Morpholines
• Neuroprotective Agents
• 2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate

Topics

• Analysis of Variance
• Animals
• Blood Gas Analysis
• Brain Infarction (etiology, prevention & control)
• Cytokines (metabolism)
• Disease Models, Animal
• Encephalitis (drug therapy, etiology)
• Enzyme-Linked Immunosorbent Assay (methods)
• Extremities (physiopathology)
• Infarction, Middle Cerebral Artery (complications)
• Laser-Doppler Flowmetry
• Male
• Morpholines (therapeutic use)
• Nervous System Diseases (etiology, prevention & control)
• Neuroprotective Agents (therapeutic use)
• Rats
• Rats, Wistar
• Reaction Time (drug effects)
• Regional Blood Flow (drug effects)
• Time Factors
• Touch (physiology)