Low-level laser therapy 810-nm up-regulates macrophage secretion of neurotrophic factors via PKA-CREB and promotes neuronal axon regeneration in vitro.

Macrophages play key roles in the secondary injury stage of spinal cord injury (SCI). M1 macrophages occupy the lesion area and secrete high levels of inflammatory factors that hinder lesion repair, and M2 macrophages can secrete neurotrophic factors and promote axonal regeneration. The regulation of macrophage secretion after SCI is critical for injury repair. Low-level laser therapy (810-nm) (LLLT) can boost functional rehabilitation in rats after SCI; however, the mechanisms remain unclear. To explore this issue, we established an in vitro model of low-level laser irradiation of M1 macrophages, and the effects of LLLT on M1 macrophage polarization and neurotrophic factor secretion and the related mechanisms were investigated. The results showed that LLLT irradiation decreased the expression of M1 macrophage-specific markers, and increased the expression of M2 macrophage-specific markers. Through forward and reverse experiments, we verified that LLLT can promote the secretion of various neurotrophic factors by activating the PKA-CREB pathway in macrophages and finally promote the regeneration of axons. Accordingly, LLLT may be an effective therapeutic approach for SCI with clinical application prospects.

Zhang J ，Sun J ，Zheng Q ，Hu X ，Wang Z ，Liang Z ，Li K ，Song J ，Ding T ，Shen X ，Zhang J ，Qiao L ... -  《-》

Photobiomodulation Promotes Neuronal Axon Regeneration After Oxidative Stress and Induces a Change in Polarization from M1 to M2 in Macrophages via Stimulation of CCL2 in Neurons: Relevance to Spinal Cord Injury.

Zheng Q ，Zhang J ，Zuo X ，Sun J ，Liang Z ，Hu X ，Wang Z ，Li K ，Song J ，Ding T ，Shen X ，Ma Y ，Li P ... -  《-》

Aldose Reductase Regulates Microglia/Macrophages Polarization Through the cAMP Response Element-Binding Protein After Spinal Cord Injury in Mice.

Zhang Q ，Bian G ，Chen P ，Liu L ，Yu C ，Liu F ，Xue Q ，Chung SK ，Song B ，Ju G ，Wang J ... -  《-》

[The 810 nm low-level laser inhibits the polarization of M1 bone marrow-derived macrophages to promote neuronal axon growth of dorsal root ganglion].

Dai C ，Sun J ，Zhang J ，Liang Z ，Wang Z ，Hu X ，Luo Z ... -  《-》

Ginsenoside Rb1 Promotes Motor Functional Recovery and Axonal Regeneration in Post-stroke Mice through cAMP/PKA/CREB Signaling Pathway.

The central nervous system (CNS) has a poor self-repairing capability after injury because of the inhibition of axonal regeneration by many myelin-associated inhibitory factors. Therefore, ischemic stroke usually leads to disability. Previous studies reported that Ginsenoside Rb1 (GRb1) plays a role in neuronal protection in acute phase after ischemic stroke, but its efficacy in post-stroke and the underlying mechanism are not clear. Recent evidences demonstrated GRb1 promotes neurotransmitter release through the cAMP-depend protein kinase A (PKA) pathway, which is related to axonal regeneration. The present study aimed to determine whether GRb1 improves long-term motor functional recovery and promotes cortical axon regeneration in post-stroke. Adult male C57BL/6 mice were subjected to distal middle cerebral artery occlusion (dMCAO). GRb1 solution (5 mg/ml) or equal volume of normal saline was injected intraperitoneally for the first time at 24 h after surgery, and then daily injected until day 14. Day 3, 7, 14 and 28 after dMCAO were used as observation time points. Motor functional recovery was assessed with Rota-rod test and grid walking task. The expression of growth-associated protein 43 (GAP43) and biotinylated dextran amine (BDA) was measured to evaluate axonal regeneration. The levels of cyclic AMP (cAMP) and PKA were measured by Elisa, PKAc and phosphorylated cAMP response element protein (pCREB) were determined by western blot. Our results shown that GRb1 treatment improved motor function and increased the expression of GAP43 and BDA in ipsilesional and contralateral cortex. GRb1 significantly elevated cAMP and PKA, increased the protein expression of PKAc and pCREB. However, the effects of GRb1 were eliminated by H89 intervention (a PKA inhibitor). These results suggested that GRb1 improved functional recovery in post-stroke by stimulating axonal regeneration and brain repair. The underlying mechanism might be up-regulating the expression of cAMP/PKA/CREB pathway.

Gao X ，Zhang X ，Cui L ，Chen R ，Zhang C ，Xue J ，Zhang L ，He W ，Li J ，Wei S ，Wei M ，Cui H ... -  《-》