Bonova Petra, Danielisova Viera, Nemethova Miroslava, Matiasova Milina, Bona Martin, Gottlieb Miroslav
Institute of Neurobiology, Slovak Academy of Sciences, Košice, Slovakia,
J Mol Neurosci. 2015 Sep;57(1):73-82. doi: 10.1007/s12031-015-0578-6. Epub 2015 May 14.
The impact of therapeutic intervention in stroke depends on its appropriate timing during infarct evolution. We have studied markers of brain tissue damage initiated by permanent occlusion of the middle cerebral artery (MCAO) at three time points during which the infarct spread (1, 3 and 6 h). Based on Evans Blue extravasation and immunohistochemical detection of neurons, we confirmed continuous disruption of blood-brain barrier and loss of neurons in the ischaemic hemisphere that peaked at the sixth hour, especially in the core. Glutamate content started to rise dramatically in the entire hemisphere during the first 3 h; the highest level was determined in the core 6 h after MCAO (141 % increase). Moreover, the enzyme antioxidant defence grew by about 42 % since the first hour in the ipsilateral penumbra. Enzymes of the apoptotic pathway as well as mitochondrial enzyme release were detected since the third hour of MCAO in the ischaemic hemisphere; all achieved their maxima in the penumbra during both time periods (except cytochrome C). In conclusion, the preserved integrity of mitochondrial membrane and incompletely developed process of apoptosis may contribute to the better therapeutic outcome after ischaemic attack; however, a whole brain response should not be omitted.
治疗性干预对中风的影响取决于其在梗死演变过程中的适当时间。我们研究了大脑中动脉永久性闭塞（MCAO）在梗死扩散的三个时间点（1、3和6小时）引发的脑组织损伤标志物。基于伊文思蓝外渗和神经元的免疫组织化学检测，我们证实了缺血半球血脑屏障的持续破坏和神经元的丢失，在第6小时达到峰值，尤其是在梗死核心区。谷氨酸含量在最初3小时内开始在整个半球显著升高；在MCAO后6小时梗死核心区谷氨酸含量达到最高水平（增加141%）。此外，自第一小时起同侧半暗带中酶抗氧化防御增加约42%。自MCAO后第3小时起在缺血半球检测到凋亡途径的酶以及线粒体酶释放；在两个时间段内所有这些酶在半暗带中均达到最大值（细胞色素C除外）。总之，线粒体膜的完整性保留以及凋亡过程未完全发展可能有助于缺血发作后获得更好的治疗效果；然而，全脑反应也不应被忽视。
