Objective: 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.
Methods: In the present study, the 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 24hrs after stroke. The infarct volume and behavioural tests were conducted and cytokine levels (ILs-1? and ß, IL-2, IL-4, IL-6, IL-10, GM-CSF and TNF-?) were measured in ischemic and non-ischemic cortices. The axonal damage was determined by using the pNF-H ELISA assay.
Results: The treatment with PRE-084 afforded neuroprotection following embolic stroke as evidenced by significantly reduced infarct volume and improved behavioural outcomes. Remarkably, the treatment with PRE-084 reduced levels of pro-inşammatory cytokines and enhanced anti-inşammatory cytokines. The levels of pNF-H were lower in rats treated with PRE-084 suggesting reduced axonal damage, but this finding did not reach statistical significance.
Conclusions: 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.