Inhibition of NF-κB Signaling Pathway by Resveratrol Improves Spinal Cord Injury

Spinal cord injury (SCI) can have a significant impact on an individual’s life. Herein, we discuss how resveratrol improves SCI by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Evidences show resveratrol suppresses NF-κB signaling pathway to exert its beneficial effects on various diseases. NF-κB signaling pathway plays a significant role in the pathophysiological mechanisms of SCI including increase in inflammation, augmentation of damage caused by free radicals and lipid peroxidation as well as facilitation of apoptosis and axonal demyelination. We also discuss mechanisms between resveratrol and NF-κB signaling pathway in the wake of SCI, which can be potential targets for resveratrol to treat SCI

Combinational Treatment of Bioscaffolds and Extracellular Vesicles in Spinal Cord Injury

Spinal cord injury (SCI) can result in an irreversible disability due to loss of sensorimotor function below the lesion. Presently, clinical treatments for SCI mainly include surgery, drugs and postoperative rehabilitation. The prospective roles of bioscaffolds and exosomes in several neurological diseases have been reported. Bioscaffolds can reconnect lesion gaps as well as transport cells and bioactive factors, which in turn can improve axonal and functional regeneration. Herein, we explicate the respective roles of bioscaffolds and exosomes in SCI, and elucidate on the usage of combinational therapy involving bioscaffolds and extracellular vesicles (EVs) in improving SCI

Inhibition of Autophagy in Microglia Alters Depressive-Like Behavior via BDNF Pathway in Postpartum Depression

Postpartum depression (PPD) is associated with mood disorders and elevated inflammation. Studies have evidenced the activation/inhibition of autophagy and excessive activation of microglia to have a close relationship with depression. C57 and microglia-specific autophagy-deficient mice (Cx3Cr1Cre/+ATG5loxp/loxp) were employed to establish the chronic unpredicted mild stress depression mice model from embryonic day 7 (E7) to embryonic day 16 (E16). Fluoxetine was administered for 3 weeks (commencing from 1 week after birth). Behavioral tests (open field, forced swimming, and sucrose preference tests) were implemented. Western blot and immunofluorescence staining were employed to assess the brain-derived neurotrophic factor (BDNF) expression level, autophagy-associated proteins, and inflammatory factors. Depressive behavior was reversed following fluoxetine treatment; this was evidenced via open field, sucrose preference, and forced swimming tests. Both BDNF and autophagy-associated proteins (ATG5, Beclin-1, and LC3II) were upregulated following fluoxetine treatment. Inflammatory factors including nuclear factor kappa B and inducible nitric oxide synthase were reduced while anti-inflammatory factor interleukin-10 (IL-10) was increased after fluoxetine treatment. Microglia-specific autophagy-deficient mice (Cx3Cr1Cre/+ATG5loxp/loxp) showed a curtailed autophagy level, higher inflammatory level, and reduced BDNF expression when compared with C57 mice. Autophagy inhibition in microglia contributes to inflammation, which further instigates PPD. Fluoxetine might mediate its antidepressant effect in PPD through the autophagic pathway while upregulating BDNF expression. In view of this, regulating BDNF in microglia is a potential novel therapy target for PPD

Beneficial Effects of Resveratrol-Mediated Inhibition of the mTOR Pathway in Spinal Cord Injury

Spinal cord injury (SCI) causes a high rate of morbidity and disability. The clinical features of SCI are divided into acute, subacute, and chronic phases according to its pathophysiological events. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in cell death and inflammation in the acute phase and neuroregeneration in the subacute/chronic phases at different times. Resveratrol has the potential of regulating cell growth, proliferation, metabolism, and angiogenesis through the mTOR signaling pathway. Herein, we explicate the role of resveratrol in the repair of SCI through the inhibition of the mTOR signaling pathway. The inhibition of the mTOR pathway by resveratrol has the potential of serving as a neuronal restorative mechanism following SCI

Beneficial Effects of Resveratrol-Mediated Inhibition of the mTOR Pathway in Spinal Cord Injury

Spinal cord injury (SCI) causes a high rate of morbidity and disability. The clinical features of SCI are divided into acute, subacute, and chronic phases according to its pathophysiological events. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in cell death and inflammation in the acute phase and neuroregeneration in the subacute/chronic phases at different times. Resveratrol has the potential of regulating cell growth, proliferation, metabolism, and angiogenesis through the mTOR signaling pathway. Herein, we explicate the role of resveratrol in the repair of SCI through the inhibition of the mTOR signaling pathway. The inhibition of the mTOR pathway by resveratrol has the potential of serving as a neuronal restorative mechanism following SCI

Combinational Pretreatment of Colony-Stimulating Factor 1 Receptor Inhibitor and Triptolide Upregulates BDNF-Akt and Autophagic Pathways to Improve Cerebral Ischemia

Ki20227, a selective inhibitor of colony-stimulating factor 1 receptor (CSF1R), has been suggested to regulate microglia inflammatory function and neuronal synaptic plasticity. Triptolide (TP) pretreatment has neuroprotective effects through its anti-inflammatory and antiapoptotic features in ischemic stroke mice. However, the underlying mechanism and pathway are presently unclear. We thus investigated the association between neuroprotective effects of combined TP and Ki20227 and BDNF-Akt and autophagy pathways. Ki20227 was administrated for 7 days, and TP was administered once 24 hours prior to building the ischemic stroke model in C57BL/6 mice. Behavioral tests, Golgi staining, immunofluorescence, and western blot analyses were employed to examine neuroprotective effects of TP and Ki20227. TP and Ki20227 pretreatments improved the neurobehavioral function in stroke mice. Synaptic protein expressions and density of dendritic spine density were upregulated in Ki20227 and TP pretreated stroke mice. Further, optimized integration of TP and Ki20227 pretreatments upregulated the NeuN expression and downregulated Iba1 expression after stroke. In addition, both TP and Ki20227 pretreatments significantly upregulated BDNF, p-Akt/Akt, and Erk1/2 protein expressions and autophagy related proteins (LC3II/I, Atg5, and p62), indicating the activation of BDNF and autophagic pathways. Optimized integration of TP and Ki20227 can improve cerebral ischemia by inhibiting CSF1R signal and trigger autophagy and BDNF-Akt signaling pathways to increase dendritic spine density and synaptic protein expressions, which in turn enhances neurobehavioral function

Hypoxia Inducible Factor-1α Attenuates Ischemic Brain Damage by Modulating Inflammatory Response and Glial Activity

Hypoxia-inducible factor 1 can sufficiently control the progress of neurological symptoms after ischemic stroke owing to their actions associated with its downstream genes. In this study, we evaluated the role of HIF-1α in attenuating brain damage after endothelin-1 injection. Focal cerebral ischemia in mice were induced by endothelin-1 microinjection. Hypoxia-inducible factor 1 activator, dimethyloxalylglycine (DMOG), and HIF-1α inhibitor, acriflavine (ACF), were used to evaluate the hypoxia-inducible factor 1 activity during cerebral ischemia. The expression levels of HIF-1α, glial fibrillary acidic protein (GFAP), interleukin-10 (IL-10), inducible nitric oxide synthase (iNOS), phosphorylated I-kappa-B-alpha/total I-kappa-B-alpha (p-IκBα/IκBα) and nuclear factor kappa B (NF-kB) were assessed. Besides, mRNA levels of IL-10, tumor necrosis factor- alpha (TNF-α), and NF-kB were also analyzed. Results showed a noticeable increase in hypoxia-inducible factor 1 and IL-10 levels in the DMOG group with a decline in iNOS, TNF-α, and NF-kB levels, implying the anti-inflammatory role of hypoxia-inducible factor 1 activator following stroke. These findings were further corroborated by GFAP immunostaining that showed astrocytic activation to be inhibited 12 days post-ischemia, as well as histological and TEM analyses that demonstrated hypoxia-inducible factor 1 induction to alleviate neuronal soma damage and cell death. Based on our study, HIF-1α could be a potential therapeutic target for ischemic stroke