Morega Shandiz, Gresita Andrei, Mitran Smaranda Ioana, Musat Madalina Iuliana, Boboc Ianis Kevyn Stefan, Gheorman Victor, Udristoiu Ion, Albu Carmen Valeria, Streba Costin Teodor, Catalin Bogdan, Rogoveanu Ion
U.M.F. Doctoral School Craiova, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.
Experimental Research Centre for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.
Life (Basel). 2022 Nov 4;12(11):1791. doi: 10.3390/life12111791.
The treatment of acute life-threatening events in patients suffering from chronic pathologies is problematic, as physicians need to consider multisystemic drug effects. Regarding Cerebrolysin, a Sonic Hedgehog signaling pathway amplifier and one of the few approved neurotrophic treatments for stroke patients, concerns of excessive Hedgehog pathway activation that could accelerate NAFLD progression to cirrhosis seem valid. We investigated stroke patients treated with Cerebrolysin that presented elevated levels of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT). We also investigated the efficiency of Cerebrolysin in reversing the neurogenesis inhibition within the hippocampus in a mouse model of NAFLD by evaluating behavior and histological outcomes. NeuN, BrdU and Iba1 positive signals in the cortex and hippocampus of the animals were also observed. Clinically, Cerebrolysin improved AST levels in a majority of stroke patients with hepatic damage. The same treatment in an experimental setup was able to reverse anxiety-like behavior in MCD mice, reducing their freezing time from 333.61 ± 21.81 s in MCD animals to 229.17 ± 26.28 in treated ones. The use of Cerebrolysin did not improve short-term memory nor rescued cell multiplication in the hippocampus after MCD food intake. Understanding the neuroprotective and neurotrophic effects that drugs have on NAFLD patients can significantly contribute to a suitable therapeutic approach.
对于患有慢性疾病的患者,急性危及生命事件的治疗存在问题,因为医生需要考虑多系统药物效应。关于脑蛋白水解物,一种音猬因子信号通路放大器,也是为数不多的经批准用于中风患者的神经营养治疗药物之一,对其过度激活刺猬因子通路可能加速非酒精性脂肪性肝病进展为肝硬化的担忧似乎是合理的。我们调查了接受脑蛋白水解物治疗且天冬氨酸转氨酶(AST)和/或丙氨酸转氨酶(ALT)水平升高的中风患者。我们还通过评估行为和组织学结果,研究了脑蛋白水解物在非酒精性脂肪性肝病小鼠模型中逆转海马体神经发生抑制的效率。还观察了动物大脑皮层和海马体中NeuN、BrdU和Iba1阳性信号。临床上,脑蛋白水解物改善了大多数肝损伤中风患者的AST水平。在实验设置中,相同的治疗能够逆转MCD小鼠的焦虑样行为,将它们的冻结时间从MCD动物的333.61±21.81秒减少到治疗后动物的229.17±26.28秒。在摄入MCD食物后,使用脑蛋白水解物并未改善短期记忆,也未挽救海马体中的细胞增殖。了解药物对非酒精性脂肪性肝病患者的神经保护和神经营养作用,可显著有助于采取合适的治疗方法。