Sigma-1 receptor ligand PRE-084 reduced infarct volume, neurological deficits, pro-inflammatory cytokines and enhanced anti-inflammatory cytokines after embolic stroke in rats
Sigma-1 receptor ligand PRE-084 reduced infarct volume, neurological deficits, pro-inflammatory cytokines and enhanced anti-inflammatory cytokines after embolic stroke in rats
复制标题
DOI：
10.1016/j.brainresbull.2011.03.019
复制
发表时间：
2011-05-30
影响因子：
3.8
通讯作者：
Jarrott, Bevyn
中科院分区：
文献类型：
--
作者：
Allahtavakoli, Mohammad;Jarrott, Bevyn
已发现σ受体激动剂在大鼠和小鼠中提供有效的神经保护。这种神经保护作用被认为是通过抗兴奋性毒性机制介导的。神经保护和免疫调节作用的σ配体还没有研究栓塞性中风。在本研究中，使大鼠经历栓塞性中风或假中风，并且用0 -1受体激动剂PRE-084（5 mg/kg i. p.）或生理盐水载体。进行脑容量和行为测试，并在缺血和非缺血皮质中测定细胞因子水平（IL-1 α和β、IL-2、IL-4、IL-6、IL-10、GM-CSF和TNF-α）。使用pNE-H ELISA测定确定轴突损伤。用PRE-084治疗在栓塞性中风后提供神经保护，如通过显著减少的梗死体积和改善的行为结果所证明的。值得注意的是，用PRE-084治疗降低了促炎细胞因子的水平并增强了抗炎细胞因子。在用PRE-084处理的大鼠中pNF-H的水平较低，表明轴突损伤减少，但该发现未达到统计学显著性。本研究的结果表明，sigma-1受体激动剂的神经保护作用的一部分可能是通过对中风后细胞因子释放的双重作用介导的。(C)2011 Elsevier Inc. All rights reserved.
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 (5 mg/kg i.p.) or saline vehicle 3 and 24 h after stroke. Infarct volume and behavioural tests were conducted, and cytokine levels (ILs-1 alpha and beta, IL-2, IL-4, IL-6, IL-10, GM-CSF and TNF-alpha) were determined in ischemic and non-ischemic cortices. Axonal damage was determined using the pNE-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. (C) 2011 Elsevier Inc. All rights reserved.