MEASUREMENT OF STRIATAL H2O2 BY MICRODIALYSIS FOLLOWING GLOBAL FOREBRAIN ISCHEMIA AND REPERFUSION IN THE RAT - CORRELATION WITH THE CYTOTOXIC POTENTIAL OF H2O2 IN-VITRO
MEASUREMENT OF STRIATAL H2O2 BY MICRODIALYSIS FOLLOWING GLOBAL FOREBRAIN ISCHEMIA AND REPERFUSION IN THE RAT - CORRELATION WITH THE CYTOTOXIC POTENTIAL OF H2O2 IN-VITRO
复制标题
DOI：
10.1016/0006-8993(94)01291-o
复制
发表时间：
1995-02-13
期刊：
影响因子：
2.9
通讯作者：
PHEBUS, LA
中科院分区：
文献类型：
--
作者：
HYSLOP, PA;ZHANG, ZY;PHEBUS, LA
毒性活性氧被认为是缺血器官再灌注后组织损伤的重要介质。当大鼠进行30分钟的全前脑缺血，24小时后，这种侮辱，有大量的损失中型神经元显示的前脑纹状体区的组织切片。本研究的目的是利用微透析直接测量一个更稳定的中间体，减少分子氧，H2 O2在大鼠纹状体4血管闭塞和再灌注后，并将这些水平与H2 O2的毒性培养中生长的神经元。纹状体H2 O2水平的显着上升，观察约1小时，在再灌注期间，相当于增加约100 μ M的峰值。在对照实验中，透析探头嵌入纹状体周围的皮质区域（其中没有由于缺血发作导致的神经元损失），组织H2 O2水平没有可测量的增加。先前已经证明过氧化氢是神经毒性的PC 12细胞，以及大鼠原代海马神经元在相当的浓度纹状体神经元的经验，在再灌注。我们证明，过氧化氢也是神经毒性的人皮质神经元细胞系，HCN-1A。这些实验建立了一个重要的联系氧化剂的产生和神经元的损失，在这个组织后，全前脑缺血。
Toxic reactive oxygen species have been implicated as important mediators of tissue injury after reperfusion of ischemic organs. When rats are subject to 30 min global forebrain ischemia, 24 h following this insult, there is substantial loss of medium-sized neurones as revealed by histological sectioning of the striatal region of the forebrain. The goal of this study was to utilize microdialysis to directly measure one of the more stable intermediates of reduced molecular oxygen, H2O2 in the rat striatum following 4-vessel occlusion and reperfusion, and to correlate these levels with H2O2 toxicity to neurones grown in culture. A significant rise in striatal H2O2 levels was observed for about 1 h during reperfusion, amounting to an increase of approximately 100 mu M at the peak. In control experiments where the dialysis probe was embedded in cortical regions surrounding the striatum (where there is no neuronal loss due to the ischemic episode), there was no measurable increase in tissue H2O2 levels. H2O2 has been previously shown to be neurotoxic to PC12 cells as well as rat primary hippocampal neurones at comparable concentrations striatal neurones experience during reperfusion. We demonstrate that H2O2 is also neurotoxic to the human cortical neuronal cell line, HCN-1A. These experiments establish an important link between oxidant generation and neuronal loss in this tissue following global forebrain ischemia.