Selakovic Vesna, Korenic Andrej, Radenovic Lidija
Institute for Medical Research, MMA, Belgrade, Serbia.
Int J Dev Neurosci. 2011 Oct;29(6):645-54. doi: 10.1016/j.ijdevneu.2011.02.009. Epub 2011 Mar 5.
The present study was undertaken to examine spatial and temporal patterns of oxidative stress rate in the brain of Mongolian gerbils submitted to different duration of global ischemia/reperfusion. The common carotid arteries of gerbils were occluded for 5, 10, or 15 min. We followed the temporal ischemia-induced oxidative stress rate, the most important factor that exacerbates brain damage by reperfusion, starting from 24 h up to 28 days after reperfusion. The spatial ischemia-induced oxidative stress distribution was measured parallely in different brain regions: forebrain cortex, striatum, hippocampus and cerebellum. Post-ischemic effects were followed in vivo by monitoring the neurological status of whole animals and at the intracellular level by standard biochemical assays in different brain regions. We measured superoxide production, superoxide dismutase activity, nitric oxide production, index of lipid peroxidation, and reduced glutathione. Our results revealed a pattern of dynamic changes in each oxidative stress parameter that corresponded with ischemia duration in all tested brain structures. The highest levels were obtained in the first 24h after the insult. After that, they slowly returned to nearly control values 28 days after reperfusion (with the exception of SOD activity that returned to control values at fourth day after reperfusion). The most sensitive oxidative stress parameter was index of lipid peroxidation. Our study confirmed spatial distribution of ischemia-induced oxidative stress. Tested brain structures showed different sensitivity to each oxidative stress parameter, although their basal levels were similar. These new findings could be valuable for creation and strategy of post-ischemic therapy.
本研究旨在检测接受不同时长全脑缺血/再灌注的蒙古沙鼠大脑中氧化应激率的时空模式。将沙鼠的双侧颈总动脉分别阻断5、10或15分钟。我们追踪了缺血诱导的氧化应激率随时间的变化情况,这是再灌注加重脑损伤的最重要因素,从再灌注后24小时直至28天进行监测。同时在不同脑区平行测量缺血诱导的氧化应激空间分布:前脑皮质、纹状体、海马体和小脑。通过监测整个动物的神经状态在体内追踪缺血后效应,并通过不同脑区的标准生化检测在细胞内水平进行追踪。我们测量了超氧化物生成、超氧化物歧化酶活性、一氧化氮生成、脂质过氧化指数和还原型谷胱甘肽。我们的结果揭示了每个氧化应激参数的动态变化模式,这与所有测试脑结构中的缺血持续时间相对应。在损伤后的最初24小时内获得最高水平。之后,它们在再灌注28天后缓慢恢复至接近对照值(超氧化物歧化酶活性除外,其在再灌注后第四天恢复至对照值)。最敏感的氧化应激参数是脂质过氧化指数。我们的研究证实了缺血诱导的氧化应激的空间分布。尽管测试脑结构的基础水平相似,但它们对每个氧化应激参数表现出不同的敏感性。这些新发现对于缺血后治疗的创建和策略可能具有重要价值。