Inflammation and neuronal apoptosis aggravate the secondary damage after spinal cord injury (SCI). Rehmannioside A (Rea) is a bioactive herbal extract isolated from Rehmanniae radix with low toxicity and neuroprotection effects. Rea treatment inhibited the release of pro‐inflammatory mediators from microglial cells, and promoted M2 polarization in vitro, which in turn protected the co‐cultured neurons from apoptosis via suppression of the NF‐κB and MAPK signalling pathways. Furthermore, daily intraperitoneal injections of 80 mg/kg Rea into a rat model of SCI significantly improved the behavioural and histological indices, promoted M2 microglial polarization, alleviated neuronal apoptosis, and increased motor function recovery. Therefore, Rea is a promising therapeutic option for SCI and should be clinically explored.

Tendon injuries are common and require a long time to heal, and are particularly associated with some adverse problems such as adhesion and rupture. Herein, we aim to develop new bioactive scaffolds endowed with stem cell sheets and growth factors to enable cell migration and proliferation favorable for tendon regeneration in situ. An exogenous basic fibroblast growth factor (bFGF)-loaded fibrin gel was firstly incorporated into the porous network of knitted poly(lactide-co-glycolide) (PLGA) scaffolds and then sheets of mesenchymal stem cells (MSCs) were also integrated into the scaffolds. It was shown that the pores in the knitted PLGA scaffold were readily filled with a complex network of fibrin fiber gel and the fibrin fibers were beneficial for the controlled release of bFGF over a long time period. After transplantation in a critical-size Achilles tendon defect model (7 mm) in the rat right hindlimb, gross observation revealed no immunologic incompatibility or rejection derived from the scaffold systems. It was observed that the MSC sheets contributed directly to tendon regeneration, and exerted an environment-modifying effect on the injuries in situ, consistent with the beneficial effect of bFGF. It was interesting that the knitted PLGA–fibrin gel scaffolds loaded with MSC sheets and bFGF showed the highest expression of tendon-related gene markers and outstanding repair efficacy, including appreciable biomechanical strength and native-like histological microstructures. Therefore, the integration of MSC sheets and bFGF into PLGA/bFGF–fibrin gel scaffolds may stimulate the proliferation and tenogenic differentiation of MSCs in situ and synergistically enhance the injured tendon reconstruction.

Objective: Spinal cord injury (SCI) is a common injury that seriously threatens human health. NF-κB may be involved in the secondary injury of SCI that is mediated by inflammation and aggravates damage. Our study was aimed to investigate the role of NF-κB signaling in DUSP19-mediated cleaved Caspase-3 expression and the release of inflammatory factors in vivo and in vitro. Materials and Methods: DUSP19 mRNA expression and the content of IL-6 and IL-8 in patients with traumatic SCI (TSCI) were measured by real-time PCR and ELISA, respectively. The levels of p-NF-κBp65, NF-κBp65 and cleaved Caspase-3 expression and the concentrations of IL-6 and IL-8 were measured by western blotting and ELISA, respectively. Results: Patients with TSCI showed lower DUSP19 expression and higher concentration of IL-6 and IL-8 compared with healthy controls. DUSP19 overexpression inhibited p-NF-κBp65 level, cleaved Caspase-3 expression, and production of IL-8 and IL-6 in the mice induced by TSCI. DUSP19 silencing increased p-NF-κBp65 level, cleaved Caspase-3 expression, and concentration of IL-6 and IL-8 in mouse primary microglia cells. DUSP19 overexpression had an inverse effect. Importantly, DUSP19 silencing and overexpression mediated p-NF-κBp65 level, cleaved Caspase-3 expression, and concentration of IL-6 and IL-8 in mouse primary microglia cells were reversed by NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) and NF-κB activator 12-myristate 13-acetate (PMA), respectively. Conclusion: These results suggested that DUSP19-mediated SCI-induced apoptosis and inflammation via NF-κB signaling and might therefore serve as a potential therapeutic target for SCI.

Lysosomes are degradative, metabolic and signaling organelles in central nervous system (CNS) cells and play essential roles in neural homeostasis, injury responses and disease progression. Changes in lysosomal function are required for neurons, microglia, astrocytes and oligodendrocyte-lineage cells to adapt to proteotoxic stress, lipid overload, mitochondrial damage and inflammatory stimulation. Therefore, lysosomal activity in the CNS is regulated by diverse chemical and cellular cues, including luminal acidification, hydrolase maturation, ion transport, membrane integrity, lipid handling and transcriptional lysosome biogenesis. Here, we summarize current knowledge of lysosomal organization and function in neural cells, including lysosomal membrane signaling, vacuolar H ⁺ -ATPase (V-ATPase)-dependent acidification, ion and redox regulation, lysosomal membrane quality control, and metabolic recycling of proteins, lipids, glycans and damaged organelles. We then survey pathological lysosomal remodeling in spinal cord injury, traumatic brain injury, Alzheimer’s disease, Parkinson’s disease and related neurological disorders. Across these conditions, lysosomal remodeling may initially support cargo clearance and stress adaptation, but becomes maladaptive when degradative capacity, membrane repair or lipid-processing ability fails to meet cellular demand. Finally, we discuss lysosome-oriented therapeutic strategies for neural repair, including restoration of lysosomal acidification and hydrolase activity, transcription factor EB/transcription factor E3 (TFEB/TFE3)-mediated lysosomal biogenesis, regulation of lysosomal ion channels, enhancement of myelin lipid turnover, and lysosome-responsive nanomedicine. This Review highlights lysosomes as active organizers of CNS injury and repair rather than passive endpoints of degradation.