Semyachkina-Glushkovskaya Oxana, Borisova Ekaterina, Abakumov Maxim, Gorin Dmitry, Avramov Latchezar, Fedosov Ivan, Namykin Anton, Abdurashitov Arkady, Serov Alexander, Pavlov Alexey, Zinchenko Ekaterina, Lychagov Vlad, Navolokin Nikita, Shirokov Alexander, Maslyakova Galina, Zhu Dan, Luo Qingming, Chekhonin Vladimir, Tuchin Valery, Kurths Jürgen
Department of Physiology of Human and Animals, Saratov State UniversitySaratov, Russia; Huazhong University of Science and TechnologyWuhan, China.
Laboratory of Biophotonics, Institute of Electronics, Bulgarian Academy of Sciences Sofia, Bulgaria.
Front Physiol. 2016 Jun 14;7:210. doi: 10.3389/fphys.2016.00210. eCollection 2016.
In this study, we analyzed the time-depended scenario of stress response cascade preceding and accompanying brain hemorrhages in newborn rats using an interdisciplinary approach based on: a morphological analysis of brain tissues, coherent-domain optical technologies for visualization of the cerebral blood flow, monitoring of the cerebral oxygenation and the deformability of red blood cells (RBCs). Using a model of stress-induced brain hemorrhages (sound stress, 120 dB, 370 Hz), we studied changes in neonatal brain 2, 4, 6, 8 h after stress (the pre-hemorrhage, latent period) and 24 h after stress (the post-hemorrhage period). We found that latent period of brain hemorrhages is accompanied by gradual pathological changes in systemic, metabolic, and cellular levels of stress. The incidence of brain hemorrhages is characterized by a progression of these changes and the irreversible cell death in the brain areas involved in higher mental functions. These processes are realized via a time-depended reduction of cerebral venous blood flow and oxygenation that was accompanied by an increase in RBCs deformability. The significant depletion of the molecular layer of the prefrontal cortex and the pyramidal neurons, which are crucial for associative learning and attention, is developed as a consequence of homeostasis imbalance. Thus, stress-induced processes preceding and accompanying brain hemorrhages in neonatal period contribute to serious injuries of the brain blood circulation, cerebral metabolic activity and structural elements of cognitive function. These results are an informative platform for further studies of mechanisms underlying stress-induced brain hemorrhages during the first days of life that will improve the future generation's health.
在本研究中,我们采用跨学科方法分析了新生大鼠脑出血前后应激反应级联的时间依赖性情况,该方法基于:脑组织的形态学分析、用于可视化脑血流的相干域光学技术、脑氧合监测以及红细胞(RBC)的变形性监测。使用应激诱导脑出血模型(声音应激,120分贝,370赫兹),我们研究了应激后2、4、6、8小时(出血前期、潜伏期)和应激后24小时(出血后期)新生大鼠脑内的变化。我们发现,脑出血的潜伏期伴随着应激在全身、代谢和细胞水平上的逐渐病理变化。脑出血的发生率表现为这些变化的进展以及参与高级心理功能的脑区中不可逆的细胞死亡。这些过程是通过脑静脉血流和氧合的时间依赖性减少来实现的,同时红细胞变形性增加。前额叶皮质分子层和锥体神经元的显著耗竭是体内平衡失衡的结果,而前额叶皮质分子层和锥体神经元对联想学习和注意力至关重要。因此,新生儿期脑出血前后的应激诱导过程会导致脑血液循环、脑代谢活动以及认知功能结构要素的严重损伤。这些结果为进一步研究生命最初几天应激诱导脑出血的潜在机制提供了信息平台,这将改善后代的健康。