Nicotinamide Improves Functional Recovery via Regulation of the RAGE/JNK/NF-κB Signaling Pathway after Brain Injury

Abstract

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.

Protection of Curcumin against Streptozocin-Induced Pancreatic Cell Destruction in T2D Rats

“…RAGE-related pathway activation may promote the overexpression of inflammatory factors and peroxides through JNK/NF-κB signaling, which participates in organ damage. In this process, the phosphorylation of JNK protein is a key link in signal pathway activation [24][25][26]. In the present study, we found that expression of RAGE, JNK, p-JNK, NF-κB, and p-NF-κB was increased in STZ-induced diabetic rats, suggesting that RAGE activation can activate JNK/NF-κB signaling through the phosphorylation pathway to participate in the apoptotic destruction of pancreatic tissue.…”

Neurological Enhancement Effects of Melatonin against Brain Injury-Induced Oxidative Stress, Neuroinflammation, and Neurodegeneration via AMPK/CREB Signaling

“…p-CREB, the target protein of p-AMPK and a regulator of neuroinflammation [50], was also significantly downregulated in the cortex and hippocampus of the rmTBI mouse brain. Activation of NF-κB has been cited in brain injuries [51]. It was interesting to observe that the treatment with melatonin reversed the energy depletion via regulating the AMPK level, as well as the pro-survival CREB proteins, in the rmTBI plus Mel-treated group, reflecting neuronal injury (Figure 1C).…”

Hesperetin, a Citrus Flavonoid, Attenuates LPS-Induced Neuroinflammation, Apoptosis and Memory Impairments by Modulating TLR4/NF-κB Signaling

“…For morphological examinations, we conducted Nissl’s staining, which indicates the number of neuronal cells loss. Briefly, as previously described [33,34], the brain slides were washed with 1% PBS (0.01 M) followed by staining with a solution of Cresyl violet (0.5%) comprising a few drops of glacial acetic acids for 8–10 min. After that, sections were washed with distilled water followed by dehydration in graded ethanol of 70%, 95%, and 100%.…”