Alam Sayed Ibrar, Rehman Shafiq Ur, Kim Myeong Ok
Division of Life Science and Applied Life Sciences (BK21), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea.
J Clin Med. 2019 Feb 22;8(2):0. doi: 10.3390/jcm8020271.
Brain injuries are a serious global health issue and are the leading cause of neurodegeneration. To date, there is no proper cure and treatment for brain-injury-induced neuropathological conditions because of a lack of sufficient knowledge and the failure to develop a drug due to the multi-pathological conditions in the brain. Herein, we explored the neurotherapeutic effects of Nicotinamide (NAM), against brain injury-induced neurodegeneration and behavioral problems. Treating injured mouse brains with NAM, for 7 days, significantly ameliorated several pathological events. Interestingly, NAM treatment significantly inhibited the injury-induced activation of receptor for advanced glycation end-products (RAGE), c-Jun N-terminal kinases (JNK), and neuroinflammatory mediators, such as NF-κB, TNF-α, IL-1β, and NOS2 in the brain, and it also regulated the levels of apoptotic markers, including Bax, caspase-3, and Bcl-2. Furthermore, treatment using NAM in TBI mice, significantly reversed synaptic protein loss and improved memory impairments and behavioral outcomes. Our findings suggested that NAM treatment reduced injury-induced secondary neurodegenerative pathology by modulating RAGE/JNK/NF-κB signaling in mice. Therefore, we recommend that NAM would be a safe and efficient therapeutic agent against brain-injury-induced neurodegeneration.
脑损伤是一个严重的全球健康问题，是神经退行性变的主要原因。迄今为止，由于缺乏足够的知识以及因大脑中的多病理状况而未能研发出药物，对于脑损伤诱导的神经病理状况尚无恰当的治愈方法和治疗手段。在此，我们探究了烟酰胺（NAM）对脑损伤诱导的神经退行性变和行为问题的神经治疗作用。用NAM处理受伤的小鼠大脑7天，显著改善了多种病理事件。有趣的是，NAM处理显著抑制了大脑中晚期糖基化终产物受体（RAGE）、c-Jun氨基末端激酶（JNK）以及神经炎症介质如NF-κB、TNF-α、IL-1β和NOS2的损伤诱导激活，并且还调节了包括Bax、半胱天冬酶-3和Bcl-2在内的凋亡标志物水平。此外，在创伤性脑损伤（TBI）小鼠中使用NAM进行治疗，显著逆转了突触蛋白损失，并改善了记忆障碍和行为结果。我们的研究结果表明，NAM处理通过调节小鼠中的RAGE/JNK/NF-κB信号传导减少了损伤诱导的继发性神经退行性病理。因此，我们建议NAM将是一种针对脑损伤诱导的神经退行性变的安全有效的治疗剂。
