Laboratory of Comparative Neuroanatomy, Dept. of Biology, Ecology and Earth Science (DiBEST), University of Calabria, Italy.
Laboratory of Cardiovascular Physiology, Dept. of Biology, Ecology & Earth Science, University of Calabria, Italy.
Neuroscience. 2018 Apr 1;375:158-168. doi: 10.1016/j.neuroscience.2018.01.067. Epub 2018 Feb 9.
It is already widely known that the different brain areas involved in blood pressure control, are highly vulnerable to the deleterious effects of this condition. Of particular concern are hypertensive and neuroinflammatory-dependent injuries that by modifying blood flow account for artery structural and functional alterations. It was thus our intention to establish if expression changes of some key brain neuroinflammatory factors like caspase-1,3, NF-kB, IL-1β and NLRP3, which are known to control blood pressure, are actively involved with inflammation regulatory events in a highly valuable spontaneously hypertensive rat (SHR) model. Indeed, notably increased (p < 0.001) caspase-1, NLRP3 and IL-1β mRNA levels were detected in amygdalar plus hypothalamic areas of SHR. Contextually, similar up-regulated levels of these factors were also reported in brainstem nuclei with respect to the few hippocampal areas. This trend was supported by moderate increases (p < 0.05) of NLRP3 in amygdalar and brainstem sites, while notably greater expression differences of NF-kB protein were observed in hippocampal and hypothalamic areas of SHR. At the same time, moderately increased levels of iNOS were typical of all of the above brain areas with the exception of the consistently (p < 0.01) increased levels featured in the brainstem. Moreover, even immunohistochemical evaluations supplied notably and moderately increased cleaved caspase-3 cell levels in hippocampus and hypothalamus areas, respectively. Overall, evident hypertensive bouts correlated to neuroinflammatory events, especially in brain areas controlling blood pressure, tend to underlie the value of novel therapeutic approaches designed to improve brain blood flow and subsequently reduce hypertensive-dependent cerebral complications.
已经广为人知的是，参与血压控制的不同脑区非常容易受到这种情况的有害影响。特别值得关注的是高血压和神经炎症依赖性损伤，这些损伤通过改变血流来解释动脉结构和功能的改变。因此，我们的目的是确定一些关键的脑神经炎症因子（如 caspase-1、3、NF-kB、IL-1β 和 NLRP3）的表达变化是否与高血压大鼠（SHR）模型中的炎症调节事件密切相关，这些因子已知可以控制血压。事实上，在 SHR 的杏仁核加下丘脑区域检测到明显增加的 caspase-1、NLRP3 和 IL-1β mRNA 水平（p < 0.001）。同时，在脑干核中也报告了这些因子的相似上调水平，而在海马区的少数区域则报道了类似的上调水平。这种趋势得到了杏仁核和脑干部位 NLRP3 适度增加（p < 0.05）的支持，而 SHR 的海马和下丘脑区域的 NF-kB 蛋白表达差异则更为显著。同时，所有上述脑区的 iNOS 水平均呈中度增加，除了脑干持续增加（p < 0.01）的水平。此外，甚至免疫组织化学评估也提供了海马体和下丘脑区域中明显和适度增加的 cleaved caspase-3 细胞水平。总的来说，明显的高血压发作与神经炎症事件相关，尤其是在控制血压的脑区，这往往是设计旨在改善脑血流并随后减少高血压相关脑并发症的新型治疗方法的价值所在。
