Therapeutics used to treat central nervous system (CNS) injury were designed to repair neurites and inhibit cell apoptosis. Previous studies have shown that neuron-derived FGF10 exerts potential neuroprotective effects after cerebral ischemia injury. However, little is known about the role of endogenous FGF10 in the recovery process after spinal cord injury (SCI). In this study, we found that FGF10 is mainly produced by neuron and microglia/macrophages, and its expression is increased after SCI. Exogenous treatment of FGF10 improved functional recovery after injury by reducing apoptosis, as well as repairing neurites via FGFR2/PI3K/Akt pathway. On another hand, inhibiting the PI3K/Akt pathway with LY294002 partially reversed the therapeutic effects of FGF10. In addition, small interfering RNA knockdown of FGFR2 suppressed PI3K/Akt pathway activation by FGF10 and abolished its anti-apoptotic and neurite repair effects in vitro. Furthermore, FGF10 treatment inhibited the activation and proliferation of microglia/macrophages through regulation of TLR4/NF-κB pathway, and attenuated the release of pro-inflammatory cytokines after SCI. Thus, the increased expression of FGF10 after acute SCI is an endogenous self-protective response, suggesting that FGF10 could be a potential treatment for CNS injury.

No abstract

Intervertebral disc degeneration (IDD) is a complicated disease in patients. The pathogenesis of IDD encompasses cellular oxidative stress, mitochondrion dysfunction and apoptosis. Melatonin eliminates oxygen free radicals, regulates mitochondrial homoeostasis and function, stimulates mitophagy and protects against cellular apoptosis. Therefore, we hypothesize that melatonin has beneficial effect on IDD by mitophagy stimulation and inhibition of apoptosis. The effects of melatonin on IDD were investigated in vitro and in vivo. For the former, melatonin diminished cellular apoptosis caused by tert‐butyl hydroperoxide in nucleus pulposus (NP) cells. Mitophagy, as well as its upstream regulator Parkin, was activated by melatonin in both a dose and time‐dependent manner. Mitophagy inhibition by cyclosporine A (CsA) partially eliminated the protective effects of melatonin against NP cell apoptosis, suggesting that mitophagy is involved in the protective effect of melatonin on IDD. In addition, melatonin was demonstrated to preserve the extracellular matrix (ECM) content of Collagen II, Aggrecan and Sox‐9, while inhibiting the expression of matrix degeneration enzymes, including MMP‐13 and ADAMTS‐5. In vivo, our results demonstrated that melatonin treatment ameliorated IDD in a puncture‐induced rat model. To conclude, our results suggested that melatonin protected NP cells against apoptosis via mitophagy induction and ameliorated disc degeneration, providing the potential therapy for IDD.

Short-segment pedicle instrumentation including the fractured vertebra was effective in treating thoracolumbar burst fractures. The loss of correction at follow-up after implant removal was associated with age, A/P ratio and anterior vertebral height < 50 %.

Acute spinal cord injury (SCI) induces severe neuroinflammation, which increases intermediary filaments and neurodegeneration. Previous studies have shown that a basic fibroblast growth factor (bFGF) and dental pulp stem cells (DPSCs) contribute to a protective effect on injured neuronal cells, but the mechanism of SCI repair is still unclear. In this study, in situ heparin (HeP) hydrogel injection containing bFGF and DPSCs (HeP-bFGF-DPSCs), as well as in vitro studies of bFGF and DPSCs, proved an effective control over inflammation. The in vivo application of HeP-bFGF-DPSCs regulated inflammatory reactions and accelerated the nerve regeneration through microtubule stabilization and tissue vasculature. Our mechanistic investigation also showed that bFGF-DPSCs treatment inhibited microglia/macrophage proliferation and activation. Furthermore, HeP-bFGF-DPSCs prevented microglia/macrophage activation and reduced proinflammatory cytokine release. In this paper, we discovered that bFGF and DPSCs worked together to attenuate tissue inflammation of the injured spinal cord, resulting in a superior nerve repair. Our results indicated that a thermosensitive hydrogel delivering bFGF and DPSCs could serve as a promising treatment option for spinal cord injuries.

Fibroblast growth factor 13 (FGF13), a nonsecretory protein of the FGF family, plays a crucial role in developing cortical neurons by stabilizing the microtubule. In previous studies, we showed that regulation of microtubule dynamics was instrumental for both growth cone initiation and for promoting regrowth of injured axon. However, the expression and effect of FGF13 in spinal cord or after spinal cord injury (SCI) remains undefined. Here, we demonstrated a role of FGF13 in regulating microtubule dynamics and in enhancing axon regeneration after SCI. Administration of FGF13 not only promoted neuronal polarization, axon formation, and growth cone initiation in vitro, but it also facilitated functional recovery following SCI. In addition, we found that upregulation of FGF13 in primary cortical neurons was accompanied by enhanced mitochondrial function, which is essential for axon regeneration. Our study has defined a novel mechanism underlying the beneficial effect of FGF13 on axon regeneration, pointing out that FGF13 may serve as a potential candidate for treating SCI or other central nervous system (CNS) injury.

Fibroblast growth factor 1 (FGF1) is thought to exert protective and regenerative effects on neurons following spinal cord injury (SCI), although the mechanism of these effects is not well understood. The use of FGF1 as a therapeutic agent is limited by its lack of physicochemical stability and its limited capacity to cross the blood‐spinal cord barrier. Here, we demonstrated that overexpression of FGF1 in spinal cord following SCI significantly reduced tissue loss, protected neurons in the ventricornu, ameliorated pathological morphology of the lesion, dramatically improved tissue recovery via neuroprotection, and promoted axonal regeneration and remyelination both in vivo and in vivo. In addition, the autophagy and the expression levels of PRDX1 (an antioxidant protein) were induced by AAV‐FGF1 in PC12 cells after H2O2 treatment. Furthermore, the autophagy levels were not changed in PRDX1‐suppressing cells that were treated by AAV‐FGF1. Taken together, these results suggest that FGF1 improves functional recovery mainly through inducing PRDX1 expression to increase autophagy and anti‐ROS activity after SCI.

Intervertebral disc degeneration (IVDD) is a chronic disease with complicated pathology involving nucleus pulposus (NP) cell apoptosis and extracellular matrix (ECM) degradation. Previous studies have shown that moderate autophagy has a protective effect against apoptosis in NP cells. Berberine (BBR) is an alkaloid compound with many beneficial properties including antimicrobial, anti-inflammatory, antioxidative, and anti-apoptotic activity. Recently, it was found to induce autophagy in various tissues as well. Thus, we hypothesized that BBR may exert a therapeutic effect on IVDD through autophagy activation. In this study, we investigated the effects of BBR on IVDD and delineated a potential mechanism. BBR treatment in vitro inhibited the expression of pro-apoptotic proteins induced by tert-butyl hydroperoxide (TBHP), and increased the expression of anti-apoptotic Bcl-2. Furthermore, it prevented ECM degradation by inhibiting the production of matrix-degrading enzymes. Additionally, BBR treatment significantly activated autophagy in NP cells. However, autophagy inhibition markedly suppressed BBR's effects on NP cell apoptosis and ECM degeneration, indicating that autophagy activation with BBR treatment is protective against IVDD. In vivo, BBR treatment increased the expression of LC3 in disc cells and prevented the development of IVDD in a needle puncture-induced rat model. Thus, BBR stimulates autophagy as a protective mechanism against NP cell apoptosis and ECM degeneration, revealing its therapeutic potential in the treatment of IVDD.