Nicotinamide Improves Functional Recovery via Regulation of the RAGE/JNK/NF-<span style="font-variant: small-caps">κ</span>B Signaling Pathway after Brain Injury

• Main Authors: Sayed Ibrar Alam, Shafiq Ur Rehman, Myeong Ok Kim
• Format: Article
• Language: English
• Published: MDPI AG 2019-02-01
• Series: Journal of Clinical Medicine
• Subjects: brain injury; nicotinamide; neurodegeneration; synaptic dysfunction; neuroinflammation
• Online Access: https://www.mdpi.com/2077-0383/8/2/271

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-&#954;B, TNF-&#945;, IL-1&#946;, 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-&#954;B signaling in mice. Therefore, we recommend that NAM would be a safe and efficient therapeutic agent against brain-injury-induced neurodegeneration.