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Background: Increasing evidence suggests that acute traumatic spinal cord injury (SCI)-induced defects in autophagy and autophagy-lysosomal pathway (ALP) may contribute to endothelial barrier disruption following injury. Recently, Kruppel-like factor 2 (KLF2) was reported as a key molecular switch on regulating autophagy. Whether KLF2 coordinates endothelial endothelial ALP in SCI is not known. Methods: Genetic manipulations of KLF2 were performed in bEnd.3 cells and SCI model. Western blot, qRT-PCR, immunofluorescence staining and Lyso-Tracker Red staining, Evans blue dye extravasation, behavioral assessment via Basso mouse scale (BMS), electrophysiology and footprint analysis were performed. Results: In SCI, autophagy flux disruption in endothelial cells contributes to TJ proteins degradation, leading to blood-spinal cord barrier (BSCB) impairment. Furthermore, the KLF2 level was decreased in SCI, overexpression of which alleviated TJ proteins loss and BSCB damage, which improve motor function recovery in SCI mice, while knockdown of KLF2 displayed the opposite effects. At the molecular level, KLF2 overexpression alleviated the TJ proteins degradation and the endothelial permeability by tuning the ALP dysfunction caused by SCI and oxygen glucose deprivation (OGD). Conclusions: Endothelial KLF2 as one of the key contributors to SCI-mediated ALP dysfunction and BSCB disruption. KLF2 could be a promising pharmacological target for the management and treatment of SCI., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

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., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Yuqin Mao et al.)

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- κ B 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- κ B 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- κ B pathway in SCI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xiaochu Feng et al.)