Abstract：
Post-stroke depression (PSD) negatively affects the prognosis of post-stroke animals. Ramelteon has neuroprotection for chronic ischemia animals, but the effect and the biological mechanism of it on PSD is still unclear. This study explored the effects of ramelteon with prophylactic administration on blood-brain barrier in rats with middle cerebral artery occlusion (MCAO) and the oxygen-glucose deprivation/reperfusion (OGD/R) bEnd.3 cells and found that ramelteon pretreatment improved the depressive-like behaviors and decreased infarct area in MCAO rats. Also, this study found ramelteon pretreatment improved viability and inhibited permeability in OGD/R cells. In addition, this study found that MCP-1, TNF-α, and IL-1 levels were raised in the MCAO rats and that occludin protein and mRNA levels were decreased in the MCAO and the OGD/R models, while the Egr-1 level was up-regulated. All of these were antagonized by ramelteon pretreatment. In addition, overexpression of Egr-1 could reverse the effect of 100 nM ramelteon pretreatment on FITC and occludin levels in OGD/R cells. In short, this study has demonstrated that the protective effect on PSD of ramelteon pretreatment on MCAO rats is related to the development of BBB permeability and that ramelteon regulates occludin to protect the BBB by inhibiting Egr-1.
摘要：
卒中后抑郁(PSD)对卒中后动物的预后有负面影响。Ramelteon对慢性缺血动物具有神经保护作用，但其对PSD的作用及其生物学机制尚不清楚。本研究探讨了预防性给药ramelteon对大脑中动脉阻塞（MCAO）大鼠和氧糖剥夺/再灌注（OGD/R）bEnd.3细胞血脑屏障的影响，发现ramelteon预处理改善了MCAO大鼠的抑郁样行为并减少了梗死面积。此外，本研究发现ramelteon预处理提高了OGD/R细胞的活力并抑制了细胞通透性。此外,这项研究发现，MCP-1，TNF-α，MCAO大鼠IL-1水平升高，MCAO和OGD/R模型中occludin蛋白和mRNA水平降低，而Egr-1水平上调。所有这些都被ramelteon预处理拮抗。此外,Egr-1的过表达可以逆转100nMramelteon预处理对OGD/R细胞FITC和occludin水平的影响。总之,本研究表明，ramelteon预处理对MCAO大鼠PSD的保护作用与BBB通透性的发展有关，ramelteon通过抑制Egr-1调节occludin保护BBB。
