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Metformin, the first medication that is often prescribed for the treatment of type 2 diabetes mellitus, was recently found to be neuroprotective. To study the mechanism underlying the neuroprotective effect of metformin, we pretreated primary spinal cord neurons with 50 [micro]M or 100 [micro]M metformin for 2 h prior to treatment with hydrogen peroxide ([H.sub.2][O.sub.2]) for up to 48 h. Our results showed that [H.sub.2][O.sub.2] increased the expression of purinergic receptor P2X7 (P2X7R) in spinal cord neurons, which promoted the downstream pro-inflammatory cytokines release and oxidative stress. We found that metformin could reverse these pro-inflammatory and pro-oxidative effects of [H.sub.2][O.sub.2]. Besides, P2X7R knockdown by siRNA suppressed [H.sub.2][O.sub.2]-induced pro-inflammatory cytokine release and oxidative stress response. In conclusion, our results show that metformin can alleviate [H.sub.2][O.sub.2]-induced inflammation and oxidative stress via modulating the P2X7R signaling pathway. Key words: metformin, inflammation, oxidative stress, spinal cord neurons. Recemment, on a montre que la metformine, le medicament contre le diabete sucre de type 2 souvent prescrit en premier, a des effets neuroprotecteurs. En vue d'etudier le mode d'action sous-jacent des effets neuroprotecteurs de la metformine, nous avons mis des neurones de moelle epiniere primaires en presence de peroxyde d'hydrogene ([H.sub.2][O.sub.2]) pendant jusqu'a 48 heures apres les avoir exposes a de la metformine a 50 ou a 100 [micro]M pendant 2 heures. Nos resultats ont montre que le [H.sub.2][O.sub.2] entrainait une augmentation de l'expression du recepteur purinergique de P2X7 (P2X7R) dans les neurones de moelle epiniere, ce qui favorisait la liberation de cytokines proinflammatoires en aval et le stress oxydatif. Nous avons observe que la metformine pouvait inverser ces effets proinflammatoires et pro-oxydatifs du [H.sub.2][O.sub.2]. Par ailleurs, la repression (<< knockdown >>) des P2X7R par siRNA permettait d'inhiber completement la liberation de cytokines proinflammatoires et la reaction de stress oxydatif engendrees par le [H.sub.2][O.sub.2]. En conclusion, nos resultats montrent que la metformine peut attenuer l'inflammation et le stress oxydatif engendres par le [H.sub.2][O.sub.2] par l'intermediaire de la modulation de la voie de signalisation des P2X7R. [Traduit par la Redaction] Mots-cles: metformine, inflammation, stress oxydatif, neurones de moelle epiniere., Introduction Spinal cord injury (SCI) is one of the devastating injuries that are commonly caused by trauma or conditions such as infection and tumor. The World Health Organization (WHO) estimates [...]

Spinal cord injury (SCI) profoundly impacts the central nervous system and significantly affects the lives and health of patients. SCI is characterized by a primary injury and subsequent secondary injury, which includes oxidative stress, inflammation, and apoptosis. Effectively addressing inflammation and apoptosis is crucial for SCI treatment. Minocycline (MnCy), while a widely used anti-inflammatory drug, suffers from limited efficacy in SCI treatments due to its poor targeting capabilities. Our research has identified that folic acid (FA) can improve the targeting of anti-inflammatory agents to macrophages through the activation of folate receptors 1 and 2. Additionally, exosomes derived from bone marrow mesenchymal stem cells (BMSCs) leverage the regenerative properties of stem cells and address the challenge of their low local survival rates. In this study, we engineered FA-modified BMSC-derived exosomes loaded with MnCy (FA-Exo-MnCy). Our in vivo imaging demonstrated that FA-Exo-MnCy specifically accumulates at the injury site, where it exerts a significant anti-inflammatory effect. Pharmacodynamic studies further confirmed that FA-Exo-MnCy effectively reduces both inflammation and apoptosis, showcasing its potential as a promising treatment option for SCI. [ABSTRACT FROM AUTHOR]

Secondary injury following spinal cord injury (SCI) results in a large production of reactive oxygen species (ROS) (e.g., H2O2) in the spinal cord microenvironment, which then leads to an excessive burst of inflammation and ultimately neuronal death. In this study, we prepared manganese dioxide (MnO2) nanoparticles coated by macrophage membranes, named M@MnO2, to cope with early ROS bursts in the SCI microenvironment. The biosafety and targeting ability of the MnO2 nanoparticles were improved through the macrophage membranes. Successful preparation of M@MnO2 was verified by transmission electron microscopy, Western blot, and dynamic light scattering. Small animal imaging showed that M@MnO2 accumulated in large quantities at the site of SCI. In the early stages of SCI, M@MnO2 effectively reduced the ROS content, as well as the hypoxia-inducible factor 1α (HIF-1α) content, malondialdehyde content, and superoxide anion content caused by ROS, further leading to a decrease in some of the proteins associated with inflammation at the site of SCI (CD11b, CD86, COX2, IL-1β, and iNOS), ultimately achieving neuroprotection and recovery of motor function. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a serious refractory disease of the central nervous system (CNS), which mostly caused by high-energy trauma. Existing interventions such as hormone shock and surgery are insufficient options, which relate to the secondary inflammation and neuronal dysfunction. Hydrogel with neuron-protective behaviors attracts tremendous attention, and black phosphorus quantum dots (BPQDs) encapsulating with Epigallocatechin-3-gallate (EGCG) hydrogels (E@BP) is designed for inflammatory modulation and SCI treatment in this study. E@BP displays good stability, biocompatibility and safety profiles. E@BP incubation alleviates lipopolysaccharide (LPS)-induced inflammation of primary neurons and enhances neuronal regeneration in vitro. Furthermore, E@BP reconstructs structural versus functional integrity of spinal cord tracts, which promotes recovery of motor neuron function in SCI rats after transplantation. Importantly, E@BP restarts the cell cycle and induces nerve regeneration. Moreover, E@BP diminishes local inflammation of SCI tissues, characterized by reducing accumulation of astrocyte, microglia, macrophages, and oligodendrocytes. Indeed, a common underlying mechanism of E@BP regulating neural regenerative and inflammatory responses is to promote the phosphorylation of key proteins related to AKT signaling pathway. Together, E@BP probably repairs SCI by reducing inflammation and promoting neuronal regeneration via the AKT signaling pathway. [ABSTRACT FROM AUTHOR]