A single dose of PPARγ agonist pioglitazone reduces cortical oxidative damage and microglial reaction following lateral fluid percussion brain injury in rats
A single dose of PPARγ agonist pioglitazone reduces cortical oxidative damage and microglial reaction following lateral fluid percussion brain injury in rats
复制标题
DOI：
10.1016/j.pnpbp.2015.01.003
复制
发表时间：
2015-06-03
影响因子：
5.6
通讯作者：
Zupan, Gordana
中科院分区：
文献类型：
--
作者：
Pilipovic, Kristina;Zupan, Zeljko;Zupan, Gordana
在各种脑损伤动物模型中观察到过氧化物酶体增殖物激活受体γ (PPAR γ)激动剂的神经保护作用。在这项研究中，我们研究了单剂量吡格列酮对大鼠外性性脑损伤（TBI）后氧化和炎症参数的影响，以及对神经变性和顶叶皮层水肿形成的影响。脑外伤后10分钟给予吡格列酮1mg /kg剂量。对照组采用假手术和载药注射。术后24 h处死大鼠，用生化和组织学方法对其顶叶皮质进行分析。脑外伤后48小时处死大鼠进行皮质水肿评估。脑外伤引起大鼠顶叶皮层脂质和蛋白质氧化损伤，谷胱甘肽过氧化物酶（GSH-Px）活性、环氧合酶-2 （COX-2）过表达、反应性星形细胞增生、小胶质细胞活化、神经变性和水肿，但未影响超氧化物歧化酶活性以及白细胞介素-1 β、白细胞介素-6和肿瘤坏死因子- α的表达。吡格列酮显著降低皮质脂质和蛋白质氧化损伤，提高GSH-Px活性，降低小胶质细胞反应。吡格列酮治疗大鼠虽然有一定程度的tbi诱导的COX-2过表达、神经变性和水肿减少，但并不显著。在受伤动物中，皮质反应性星形细胞增生未受PPAR γ激动剂的影响。这些发现表明，单剂量吡格列酮在LFPI后早期给予，可减少皮质氧化损伤，增强抗氧化防御，但抗炎作用有限，提示需要进一步研究该药物治疗TBI。(C) 2015爱思唯尔公司版权所有。
Neuroprotective actions of the peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonists have been observed in various animal models of the brain injuries. In this study we examined the effects of a single dose of pioglitazone on oxidative and inflammatory parameters as well as on neurodegeneration and the edema formation in the rat parietal cortex following traumatic brain injury (TBI) induced by the lateral fluid percussion injury (LFPI) method. Pioglitazone was administered in a dose of 1 mg/kg at 10 min after the brain trauma. The animals of the control group were sham-operated and injected by vehicle. The rats were decapitated 24 h after LFPI and their parietal cortices were analyzed by biochemical and histological methods. Cortical edema was evaluated in rats sacrificed 48 h following TBI. Brain trauma caused statistically significant oxidative damage of lipids and proteins, an increase of glutathione peroxidase (GSH-Px) activity, the cyclooxygenase-2 (COX-2) overexpression, reactive astrocytosis, the microglia activation, neurodegeneration, and edema, but it did not influence the superoxide dismutase activity and the expressions of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha in the rat parietal cortex. Pioglitazone significantly decreased the cortical lipid and protein oxidative damage, increased the GSH-Px activity and reduced microglial reaction. Although a certain degree of the TBI-induced COX-2 overexpression, neurodegeneration and edema decrease was detected in pioglitazone treated rats, it was not significant. In the injured animals, cortical reactive astrocytosis was unchanged by the tested PPAR gamma agonist. These findings demonstrate that pioglitazone, administered only in a single dose, early following LFPI, reduced cortical oxidative damage, increased antioxidant defense and had limited anti-inflammatory effect, suggesting the need for further studies of this drug in the treatment of TBI. (C) 2015 Elsevier Inc. All rights reserved.