Nicotinamide mononucleotides alleviated neurological impairment via anti-neuroinflammation in traumatic brain injury

Abstract

Traumatic brain injury (TBI) is one of the main factors of death and disability in adults with a high incidence worldwide. Nervous system injury, as the most common and serious secondary injury after TBI, determines the prognosis of TBI patients. NAD + has been confirmed to have neuroprotective effects in neurodegenerative diseases, but its role in TBI remains to be explored. In our study, nicotinamide mononucleotides (NMN), a direct precursor of NAD + , was used to explore the specific role of NAD + in rats with TBI. Our results showed that NMN administration markedly attenuated histological damages, neuronal death, brain edema, and improved neurological and cognitive deficits in TBI rats. Moreover, NMN treatment significantly suppressed activated astrocytes and microglia after TBI, and further inhibited the expressions of inflammatory factor. Besides, RNA sequencing was used to access the differently expressed genes (DEGs) and their enriched (Kyoto Encyclopedia of Genes and Genomes) KEGG pathways between Sham, TBI, and TBI+NMN. We found that 1589 genes were significantly changed in TBI and 792 genes were reversed by NMN administration. For example, inflammatory factor CCL2, toll like receptors TLR2 and TLR4, proinflammatory cytokines IL-6, IL-11 and IL1rn which were activated after TBI and were decreased by NMN treatment. GO analysis also demonstrated that inflammatory response was the most significant biological process reversed by NMN treatment. Moreover, the reversed DEGs were typically enriched in NF-Kappa B signaling pathway, Jak-STAT signaling pathway and TNF signaling pathway. Taken together, our data showed that NMN alleviated neurological impairment via anti-neuroinflammation in traumatic brain injury and the mechanisms may involve TLR2/4-NF-κB signaling.

Therapeutic application of nicotinamide: As a potential target for inhibiting fibrotic scar formation following spinal cord injury

“…Apart from that, our research results indicate that NAM has a protective effect on neuronal cell death after SCI (Figure 6), which is consistent with the research results of Zhu et al 80 . Their research results confirm that nicotinamide mononucleotides (NMN) have a protective effect on traumatic brain injury.…”

Bone Allograft Acid Lysates Change the Genetic Signature of Gingival Fibroblasts

“…It is thus possible that other pathways than canonical TGF-β signaling mediate the ALBA-induced expression of IL11, AREG, and C11orf96. For instance, IL11 expression is sensitive to oxidative stress [45], mechanical damage of chondrocyte micromass cultures [46], and traumatic brain injury [47], suggesting that damage-associated molecular patterns (DAMPs), as they are presumably present in bone allografts [48], might drive IL11 expression. Moreover, several functional elements implicated in the induction of AREG expression have been identified in the promoter [49] and AREG expression is induced through the activation of various pathways, including cAMP/PKA and protein kinase C [49].…”

Nicotinamide Deteriorates Post-Stroke Immunodepression Following Cerebral Ischemia–Reperfusion Injury in Mice

“…It is a precursor of nicotinamide adenine dinucleotide (NAD+) and a co-factor in the electron transport chain. Abundant evidence has shown that Nico is a potent neuroprotectant against cerebral ischemia [ 5 ], brain trauma [ 6 , 7 , 8 ], and neurotoxin-induced CNS damage [ 9 , 10 ]. Administering Nico enhances the energy reservoir in the brain by preventing the depletion of NAD+ consumed by nuclear enzyme poly(ADP-ribose) polymerase (PARP), a DNA repair enzyme, thereby maintaining ATP levels in the brain.…”

“…In vitro studies have revealed that Nico exhibits multiple inhibitory effects on inflammation and oxidative stress. It inhibits the production of key proinflammatory cytokines, including interleukin 6 (IL-6), IL-1 beta, tumor necrosis factor alpha (TNF-α), and IL-8 [ 8 , 11 ]. Nico also reduces the generation of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) [ 12 ] whilst scavenging free radicals [ 13 ].…”