Kosari-Nasab Morteza, Shokouhi Ghaffar, Ghorbanihaghjo Amir, Abbasi Mehran Mesgari, Salari Ali-Akbar
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Neurosurgery, Tabriz University of Medical Sciences, Tabriz, Iran; Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Toxicol Appl Pharmacol. 2018 Jan 1;338:159-173. doi: 10.1016/j.taap.2017.11.012. Epub 2017 Nov 22.
Clinical and experimental studies have shown that mild traumatic brain injury (mTBI) is associated with increased anxiety- and depression-related behaviors and inflammation in the brain. Unfortunately, there are no specific therapies for long-term behavioral consequences of mTBI. This study set out to determine whether silymarin treatment compared to diazepam (DZP) and fluoxetine (FLX) can reduce neuroinflammation, anxiety- and depression-like behaviors after mTBI induction in mice. We used open field, elevated plus maze, light-dark box, zero maze, sucrose preference, forced swim, and tail suspension tests to assess anxiety and depression-like behaviors in mTBI-induced mice. The levels of tumor necrosis factor (TNF)-α protein, a marker of inflammation, in the prefrontal cortex and hippocampus was also measured. This study identified that the long-term treatment with DZP, FLX or SIL results in decreased anxiety and depression-like behaviors in mTBI-induced mice. The results also showed that these drugs reduced TNF-α levels in the prefrontal cortex and hippocampus. In addition, there were no significant differences between the effects of SIL and DZP or SIL and FLX on behavioral and cytokine levels in mTBI-induced mice. Our findings support the idea that mTBI could be a risk factor for anxiety- and depression-related disorders and neuroinflammation in the brain. Taken together, this study demonstrates that DZP, FLX or SIL can significantly reduce anxiety- and depression-like symptoms, and neuroinflammation after mTBI induction in mice.
临床和实验研究表明，轻度创伤性脑损伤（mTBI）与大脑中焦虑和抑郁相关行为及炎症增加有关。不幸的是，对于mTBI的长期行为后果尚无特异性治疗方法。本研究旨在确定与地西泮（DZP）和氟西汀（FLX）相比，水飞蓟宾治疗是否能减轻小鼠mTBI诱导后的神经炎症、焦虑和抑郁样行为。我们使用旷场试验、高架十字迷宫试验、明暗箱试验、零迷宫试验、蔗糖偏好试验、强迫游泳试验和悬尾试验来评估mTBI诱导小鼠的焦虑和抑郁样行为。还测量了前额叶皮质和海马中炎症标志物肿瘤坏死因子（TNF）-α蛋白的水平。本研究发现，长期使用DZP、FLX或水飞蓟宾可减少mTBI诱导小鼠的焦虑和抑郁样行为。结果还表明，这些药物降低了前额叶皮质和海马中的TNF-α水平。此外，水飞蓟宾与DZP或水飞蓟宾与FLX对mTBI诱导小鼠行为和细胞因子水平的影响之间无显著差异。我们的研究结果支持mTBI可能是大脑中焦虑和抑郁相关障碍及神经炎症危险因素这一观点。综上所述，本研究表明DZP、FLX或水飞蓟宾可显著减轻小鼠mTBI诱导后的焦虑和抑郁样症状及神经炎症。
