Neuroinflammation and neuronal autophagic death were suppressed via Rosiglitazone treatment: New evidence on neuroprotection in a rat model of global cerebral ischemia
Neuroinflammation and neuronal autophagic death were suppressed via Rosiglitazone treatment: New evidence on neuroprotection in a rat model of global cerebral ischemia
复制标题
DOI：
10.1016/j.jns.2014.12.027
复制
发表时间：
2015-02-15
影响因子：
4.4
通讯作者：
Liu, Zun-Jing
中科院分区：
文献类型：
--
作者：
Shao, Zi-Qiang;Liu, Zun-Jing
缺血性脑卒中是导致死亡和残疾的主要原因之一，具有高发病率和复发率。越来越多的证据表明，自噬参与了缺血/再灌注（I/R）损伤后神经元细胞的死亡和功能丧失。过氧化物酶体增殖激活受体- γ (ppar - γ)激动剂罗格列酮（RSG）以其抗炎作用而闻名。已有研究表明，RSG在慢性脑损伤和急性脑损伤动物模型中均能发挥神经保护作用。然而，RSG治疗是否参与I/R损伤后的自噬性神经元死亡尚不清楚。本研究旨在假设RSG治疗可诱导大鼠全脑缺血（GCI）模型的神经保护特性，从而探讨其潜在机制。我们发现，GCI后立即单次注射RSG可显著减少脑梗死体积和脑水肿，并增加神经元存活率和功能恢复。这些作用与海马区炎症细胞因子和自噬相关蛋白表达的减少有关。我们的研究结果提供了体内证据，表明RSG可以显著保护大鼠免受I/R损伤引起的脑损伤，其机制可能与抑制神经炎症过程从而减轻神经元自噬死亡有关。所有数据表明，RSG可以进一步发展为缺血性脑卒中的临床神经保护候选药物。(C) 2014 Elsevier B.V.版权所有
Ischemic stroke is one of the leading causes of mortality and disability with documented high incidence and relapse rate. Accumulating evidence indicates that autophagy participated in neuronal cell death and functional loss induced following ischemia/reperfusion (I/R) injury. The peroxisome proliferating activating receptor-gamma (PPAR-gamma) agonist, Rosiglitazone (RSG), is known for its anti-inflammatory actions. Previous studies have demonstrated that RSG can exert neuroprotection in animal models of both chronic brain injuries and acute brain insults. However, whether RSG treatment is involved in the autophagic neuronal death following I/R injury remains totally unclear. The present study aimed to hypothesize that treatment of RSG could induce neuroprotective properties in a rat model of global cerebral ischemia (GCI), and thereby to investigate the underline mechanisms. We found that a single injection of RSG immediately following GCI significantly reduced cerebral infarct volume and brain edema, as well as increased neuron survival rate and function recovery. These effects correlate with a decrease of inflammatory cytokines and autophagy-associated proteins expression in the hippocampus region. Our results provide in vivo evidence that RSG significantly protected rats against I/R injury induced brain injury, and the mechanism might associate with inhibiting the processes of neuroinflammation and thereby attenuated of neuronal autophagic death. All data suggest that RSG can be further developed as a clinical neuroprotective candidate in ischemic stroke. (C) 2014 Elsevier B.V. All rights reserved.