Poly (Betulinic Acid) Nanoparticles Loaded with bFGF Improve Functional Recovery After Spinal Cord Injury.

Oxidative stress (OS) is one of the crucial molecular events of secondary spinal cord injury (SCI). Basic fibroblast growth factor (bFGF) is a multipotent cell growth factor with an anti-oxidant effect. However, bFGF has a short half-life in vivo, which limits its therapeutic application. Biodegradable polymers with excellent biocompatibility have been recently applied in SCI. The negative aspect is that polymers cannot provide a significant therapeutic effect. Betulinic acid (BA), a natural anti-inflammatory compound, has been polymerized into poly (betulinic acid) (PBA) to serve as a drug carrier for bFGF. This study explores the therapeutic effects and underlying molecular mechanisms of PBA nanoparticles (NPs) loaded with bFGF (PBA-bFGF NPs) in SCI. Results show that PBA-bFGF NPs produce remarkable biocompatibility in vivo and in vitro. The results also demonstrate that local delivery of PBA-bFGF NPs enhances motor function recovery, inhibits OS, mitigates neuroinflammation, and alleviates neuronal apoptosis following SCI. Furthermore, the results indicate that local delivery of PBA-bFGF NPs activates the nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling pathway following SCI. In summary, results suggest that local delivery of PBA-bFGF NPs delivers potential therapeutic advantages in the treatment and management of SCI.

Sesamol Attenuates Neuroinflammation by Regulating the AMPK/SIRT1/NF-κB Signaling Pathway after Spinal Cord Injury in Mice.

Inflammation is one of the crucial mechanisms mediating spinal cord injury (SCI) progress. Sesamol, a component of sesame oil, has anti-inflammatory activity, but its mechanism in SCI remains unclear. We investigated if the AMPK/SIRT1/NF-κB pathway participated in anti-inflammation of sesamol in SCI. Sesamol could inhibit neuronal apoptosis, reduce neuroinflammation, enhance M2 phenotype microglial polarization, and improved motor function recovery in mice after SCI. Furthermore, sesamol increased SIRT1 protein expression and p-AMPK/AMPK ratio, while it downregulated the p-p65/p65 ratio, indicating that sesamol treatment upregulated the AMPK/SIRT1 pathway and inhibited NF-κB activation. However, these effects were blocked by compound C which is a specific AMPK inhibitor. Together, the study suggests that sesamol is a potential drug for antineuroinflammation and improving locomotor functional recovery through regulation of the AMPK/SIRT1/NF-κB pathway in SCI.

Maltol Promotes Mitophagy and Inhibits Oxidative Stress via the Nrf2/PINK1/Parkin Pathway after Spinal Cord Injury.

Spinal cord injury (SCI), a fatal disease in the central nervous system, is characteristic of weak neuronal regeneration ability and complex pathological progress. Activation of oxidative stress (OS) and apoptosis-mediated cell death significantly contributes to the progression of SCI. Current evidence suggests that maltol exerts natural antioxidative properties via obstructing OS and apoptosis. However, the significant effect of maltol on SCI treatment has never been evaluated yet. In our current study, we explored maltol administration that could trigger the expression of Nrf2 and promote the retranslocation of Nrf2 from the cytosol to the nucleus, which can subsequently obstruct OS signal and apoptosis-mediated neuronal cell death after SCI. Furthermore, we found that maltol treatment enhances PINK1/Parkin-mediated mitophagy in PC12 cells, facilitating the recovery of mitochondrial functions. Our findings propose that maltol could be a promising therapeutic candidate for the treatment and management of SCI.