Changes in intracellular nicotinamide adenine dinucleotide (NAD⁺) levels have been observed in various disease states. A decrease in NAD⁺ levels has been noted following spinal cord injury (SCI). Nicotinamide riboside (NR) serves as the precursor of NAD⁺. Previous research has demonstrated the anti-inflammatory and apoptosis-reducing effects of NR supplements. However, it remains unclear whether NR exerts a similar role in mice after SCI. The objective of this study was to investigate the impact of NR on these changes in a mouse model of SCI. Four groups were considered: (1) non-SCI without NR (Sham), (2) non-SCI with NR (Sham +NR), (3) SCI without NR (SCI), and (4) SCI with NR (SCI + NR). Female C57BL/6J mice aged 6–8 weeks were intraperitoneally administered with 500 mg/kg/day NR for a duration of one week. The supplementation of NR resulted in a significant elevation of NAD⁺ levels in the spinal cord tissue of mice after SCI. In comparison to the SCI group, NR supplementation exhibited regulatory effects on the chemotaxis/recruitment of leukocytes, leading to reduced levels of inflammatory factors such as IL-1β, TNF-α, and IL-22 in the injured area. Moreover, NR supplementation notably enhanced the survival of neurons and synapses within the injured area, ultimately resulting in improved motor functions after SCI. Therefore, our research findings demonstrated that NR supplementation had inhibitory effects on leukocyte chemotaxis, anti-inflammatory effects, and could significantly improve the immune micro-environment after SCI, thereby promoting neuronal survival and ultimately enhancing the recovery of motor functions after SCI. NR supplementation showed promise as a potential clinical treatment strategy for SCI.

Traumatic spinal cord injury (SCI) is a common disabling condition characterized by a disrupted immune microenvironment that significantly hinders neural regeneration. In recent years, CD3⁺CD4^-CD8^- double-negative T cells (DNT cells) have garnered considerable attention due to their multifaceted roles in immune regulation. Flow cytometry data indicate a significant increase in the proportion of DNT cells following SCI. Single-cell sequencing further demonstrates the heterogeneity of DNT cells, with CD3⁺TCRαβ⁺CD4^-CD8^-NK1.1^- T cells (DNTαβ) potentially playing an immune regulatory role. Accordingly, we hypothesize that the transplantation of DNTαβ cells could improve the immune microenvironment in the spinal cord. To test this hypothesis, we obtained DNTαβ cells for SCI treatment through flow cytometric sorting. Behavioral assessments indicated that both in situ injection and tail vein injection of DNTαβ cells significantly promoted the recovery of motor function in mice with SCI. Immunohistochemical analysis further revealed that DNTαβ cells can inhibit glial proliferation and promote neuronal survival and myelination. Transcriptomic sequencing data also supported the role of DNTαβ cell transplantation in modulating immune responses through the Gzmb and IFN pathways, to promote early repair and neuroprotection following SCI. Our findings suggest that exogenous supplementation of DNTαβ cells can regulate the immune microenvironment to enhance neural regeneration after SCI, providing new therapeutic strategies and data support for cellular therapies following SCI.

Background: Spinal cord injury (SCI) patients display disruption of gut microbiome and gut dysbiosis exacerbate neurological impairment in SCI models. Cumulative data support an important role of gut microbiome in SCI. Here, we investigated the hypothesis that fecal microbiota transplantation (FMT) may exert a neuroprotective effect on SCI mice. Results: We found that FMT facilitated functional recovery, promoted neural axonal regeneration, improved animal weight gain and metabolic profiling, and enhanced intestinal barrier integrity and GI motility. High-throughput sequencing revealed that levels of phylum Firmicutes, genus Blautia, Anaerostipes and Lactobacillus were reduced in fecal samples of SCI mice, and FMT remarkably reshaped gut microbiome. Also, FMT-treated SCI mice showed increased amount of fecal short-chain fatty acids (SCFAs), which correlated with alteration of intestinal permeability and locomotor recovery. Furthermore, FMT down-regulated IL-1β/NF-κB signaling in spinal cord and NF-κB signaling in gut. Conclusion: Our study demonstrates that reprogramming of gut microbiota by FMT improves locomotor and GI functions in SCI mice, possibly through the anti-inflammatory functions of SCFAs.

Recent research advancements have revealed that phosphorylation of α-synuclein at the Serine 129 (pSer 129 α-syn, p-α-syn) possesses not only pathological implications but also significant physiological functions. However, the distribution and functions of p-α-syn in relation to lipid rafts, calcium homeostasis, and neuroinflammation warrant further investigation. In this study, we initially investigated the distribution of p-α-syn across the entire brain in both Wild-type (Wt) and Thy1-SNCA transgenic (Tg) mice. After evaluating p-α-syn levels within the cytosolic and lipid raft components of midbrain and peripheral blood cells, we identified its interaction network with CO-IP/MS in Wt group, supported by functional enrichment analyses. Subsequently, we examined calcium dynamics and inflammatory state in primary neuronal models. Our results revealed the presence of p-α-syn in midbrain and blood cells of Wt mice, where it modulated distinct protein interaction networks. Moreover, inhibiting p-α-syn did not alleviate the neuronal toxicity and calcium imbalance. Transcriptome sequencing and protein chip analysis also revealed that p-α-syn could alter the inflammatory state of neurons and significantly influence the expression and secretion of CCL2 and CCL5. Overall, this study fills a critical knowledge gap regarding p-α-syn interactomics and elucidates the essential regulatory role of p-α-syn in neuronal calcium homeostasis and neuroinflammation.

Objective: The objective was to investigate the effects of shift-work (SW) on the carotid arteries. Methods: This study used two inverted photoperiods (inverted light:dark [ILD]16:8 and ILD12:12) to create the SW model. We recorded the rhythm and performed serological tests, carotid ultrasound, magnetic resonance imaging, and carotid biopsy. Results: SW induced elevated blood pressure and increased angiotensin-II, apolipoprotein E, blood glucose, and triglycerides. SW increased the carotid intima-media thickness. SW led to the development of carotid arterial thrombosis, reduced cerebral blood flow, and increased the number of collagen fibers, expression of angiotensin receptor and low-density lipoprotein receptor in the carotid arteries. SW decreased 3-hydroxy-3-methylglutaryl-CoA reductase and nitric oxide. SW induced the atherosclerotic plaque in the aorta. Multiple results of SHR were worse than WKY rats. Conclusion: SW can induce metabolic disorders and elevated blood pressure. SW can cause intima-media thickening of the carotid artery and aorta atherosclerosis. SW may result in carotid arterial thrombosis and affect cerebral blood flow. Hypertension can aggravate the adverse effects of SW.