Experimental autoimmune neuritis (EAN) is a CD4 T-cell-mediated autoimmune inflammatory demyelinating disease of the peripheral nervous system. It has been replicated in an animal model of human inflammatory demyelinating polyradiculoneuropathy, Guillain-Barré syndrome. In this study, we evaluated the therapeutic efficacy of a selective inhibitor of the immunoproteasome subunit, low-MW polypeptide 7 (PR-957) in rats with EAN. Our results showed that PR-957 significantly delayed onset day, reduced severity and shortened duration of EAN, and alleviated demyelination and inflammatory infiltration in sciatic nerves. In addition to significantly regulating expression of the cytokine profile, PR-957 treatment down-regulated the proportion of proinflammatory T-helper (T)17 cells in sciatic nerves and spleens of rats with EAN. Data presented show the role of PR-957 in the signal transducer and activator of transcription 3 (STAT3) pathway. PR-957 not only decreased expression of IL-6 and IL-23 but also led to down-regulation of STAT3 phosphorylation in CD4 T cells. Regulation of the STAT3 pathway led to a reduction in retinoid-related orphan nuclear receptor γ t and IL-17 production. Furthermore, reduction of STAT3 phosphorylation may have directly suppressed T17-cell differentiation. Therefore, our study demonstrates that PR-957 could potently alleviate inflammation in rats with EAN and that it may be a likely candidate for treating Guillain-Barré syndrome.-Liu, H., Wan, C., Ding, Y., Han, R., He, Y., Xiao, J., Hao, J. PR-957, a selective inhibitor of immunoproteasome subunit low-MW polypeptide 7, attenuates experimental autoimmune neuritis by suppressing T17-cell differentiation and regulating cytokine production.

Physiologic ischemic exercise training can promote remote angiogenesis in the pathologic ischemic skeletal muscle and thus improve performance.

Neuronal apoptosis is the main pathological feature of spinal cord injury ( SCI ), while autophagy contributes to ameliorating neuronal damage via inhibition of apoptosis. Here, we investigated the role of tectonic family member 2 ( TCTN 2) long non‐coding RNA on apoptosis and autophagy in SCI . TCTN 2 was down‐regulated in the spinal cord tissues of a rat model of SCI and in oxygen–glucose deprivation‐induced hypoxic SY ‐ SH ‐5Y cells, while microRNA‐216b (miR‐216b) was up‐regulated. Overexpression of TCTN 2 reduced neuron apoptosis by inducing autophagy, and TCTN 2 was observed to negatively regulate miR‐216b. Furthermore, TCTN 2 promoted autophagy to repress apoptosis through the miR‐216b–Beclin‐1 pathway, and overexpression of TCTN 2 improved neurological function in the SCI rat model. In summary, our data suggest that TCTN 2 enhances autophagy by targeting the miR‐216b–Beclin‐1 pathway, thereby ameliorating neuronal apoptosis and relieving spinal cord injury.

Low-frequency pulsed electromagnetic fields (LPEMFs) have been reported to be protective for multiple diseases. However, whether the administration of LPEMFs inhibits inflammation and oxidative stress following spinal cord injury requires further investigation. In the current study, a contusion spinal cord injury model was used and LPEMFs administration was applied to investigate the molecular changes, including inflammation, oxidative stress and heat shock protein 70 (HSP70) levels. The results revealed that LPEMFs significantly promoted functional recovery following spinal cord injury, as demonstrated by an increased Basso, Beattie and Bresnahan score. The results demonstrated that LPEMFs decreased the expression of inflammatory factors, including tumor necrosis factor-α, interleukin-1β and nuclear factor-κB. Additionally, LPEMFs exposure reduced the levels of inducible nitric oxide synthase and reactive oxygen species, and upregulated the expression of catalase and superoxide dismutase. Furthermore, treatment with LPEMFs significantly enhanced the expression of HSP70 in spinal cord-injured rats. Overall, the present study revealed that LPEMFs promote functional recovery following spinal cord injury, potentially by modulating inflammation, oxidative stress and HSP70.

Objectives Our previous study indicated that aerobic exercise relieves cognitive impairment in patients with vascular cognitive impairment (VCI) via regulating brain-derived neurotrophic factor (BDNF), but the mechanism is not yet clear. This study aimed to explore whether lncRNA taurine upregulated gene 1 (TUG1) participates in the process of VCI by regulating BDNF. Methods The expressions of TUG1 and BDNF in the serum of VCI patients were detected. The potential molecular mechanisms of TUG1 in regulating hippocampal neuronal apoptosis were explored in oxygen and glucose deprivation-induced (OGD-induced) hippocampal cell line HT22. The VCI mouse model was established, and TUG1 and BDNF were overexpressed via lentivirus injection. The cognitive impairment of mice was detected by the Morris water maze experiment after the aerobic exercise. Results The level of TUG1 was elevated in the serum of VCI patients compared with the control group. The knockdown of TUG1 in OGD-induced HT22 cells increased BDNF level and decreased cell apoptosis, and the downregulation of BDNF restored the decreased cell apoptosis. RNA immunoprecipitation and RNA pull-down assays showed that TUG1 could bind to BDNF protein. The aerobic exercise alleviated cognitive impairment and inhibited hippocampal apoptosis in VCI mice. Meanwhile, the overexpression of TUG1 reversed the therapeutic effects of aerobic exercise on cognitive impairment. Conclusions The knockdown of TUG1 reduced hippocampal neuronal apoptosis and participates in the aerobic exercise-alleviated VCI, which was partly through regulating BDNF.

Background: Stroke is the leading cause of death and disability. Exercise produces neuroprotection by improving neuroplasticity. Exercise can induce exosome production. According to several studies, exosomes are involved in repairing brain function, but the relationship and mechanism of exercise, exosomes, and neuroprotection have not been elucidated. This study intends to explore the relationship and potential mechanism by observing the changes in the exosome level, infarct volume, neurological function and behavioral scores, synapses, and corticospinal tract (CST).Methods: Rats were randomly divided into four groups: a sham operation (SHAM) group, middle cerebral artery occlusion (MCAO) with sedentary intervention (SED-MCAO) group, MCAO with exercise intervention (EX-MCAO) group, and MCAO with exercise intervention and exosome injection (EX-MCAO-EXO) group. The exercise intervention was started 1 day after MCAO and lasted for 4 weeks. All rats were assessed using the modified neurological severity score (mNSS). The levels of exosomes in serum and brain, gait analysis, and magnetic resonance scan were performed 1 and 4 weeks after the intervention. After 4 weeks of intervention, the number of synapses, synaptophysin (Syn), and postsynaptic density protein 95(PSD-95) expression was detected.Results: After 4 weeks of intervention, (1) the EX-MCAO and EX-MCAO-EXO groups showed higher serum exosome (pEX−MCAO = 0.000, pEX−MCAO−EXO = 0.000) and brain exosome (pEX−MCAO = 0.001, pEX−MCAO−EXO = 0.000) levels than the SED-MCAO group, of which the EX-MCAO group had the highest serum exosome (p = 0.000) and the EX-MCAO-EXO group had the highest brain exosome (p = 0.03) levels. (2) The number of synapses in the EX-MCAO (p = 0.032) and EX-MCAO-EXO groups (p = 0.000) was significantly higher than that in the SED-MCAO group. The EX-MCAO-EXO group exhibited a greater number of synapses than the EX-MCAO (p = 0.000) group. (3) The synaptic plasticity-associated proteins were expressed significantly higher in the EX-MCAO (pSyn = 0.010, pPSD−95 = 0.044) and EX-MCAO-EXO (pSyn = 0.000, pPSD−95 = 0.000) groups than in the SED-MCAO group, and the EX-MCAO-EXO group (pSyn = 0.000, pPSD−95 = 0.046) had the highest expression. (4) Compared with the SED-MCAO group, the EX-MCAO group had significantly improved infarct volume ratio (p = 0.000), rFA value (p = 0.000), and rADC (p = 0.000). Compared with the EX-MCAO group, the EX-MCAO-EXO group had a significantly improved infarct volume ratio (p = 0.000), rFA value (p = 0.000), and rADC value (p = 0.001). (5) Compared with the SED-MCAO group, the EX-MCAO group (p = 0.001) and EX-MCAO-EXO group (p = 0.000) had significantly lower mNSS scores and improved gait. (6) The brain exosome levels were negatively correlated with the mNSS score, infarct volume ratio, and rADC value and positively correlated with the rFA value, Syn, and PSD-95 expression. The serum and brain exosome levels showed a positive correlation.Conclusions: Exercise intervention increases the serum exosome level in MCAO rats, which are recruited into the brain, leading to improved synaptic growth and CST integrity, a reduced infarct volume, and improved neurological function and gait.

Background Vascular cognitive impairment (VCI) is a common cognitive disorder caused by cerebrovascular disease, ranging from mild cognitive impairment to dementia. Studies have shown that aerobic exercise might alleviate the pathological development of VCI, and our previous study observed that aerobic exercise could alleviate VCI through NF-κB/miR-503/BDNF pathway. However, there are few studies on the mechanism. Therefore, it is of great significance to fill the gaps in the mechanism for the early diagnosis of VCI and the clinical prevention and treatment of vascular dementia. Methods CircRNA microarray analysis and quantitative real-time PCR were used to detect the expression of circRNA regulating synaptic be exocytosis 2 (RIMS2) (circRIMS2). Cell apoptosis was determined by TdT-mediated dUTP nick-end labeling (TUNEL) assay. The dual-luciferase reporter assay was performed to verify the interaction between circRIMS2 and miR-186, as well as miR-186 and BDNF. RNA pull-down assay detected the binding between circRIMS2 and miR-186. A VCI mouse model was established by repeated ligation of bilateral common carotid arteries (2VO). The lentiviral interfering vector was injected into the VCI mice through the lateral ventricle. The mice in the aerobic exercise group performed 30 min (12 m/min) running for 5 days a week. A Morris water maze test was performed after 4 weeks. Results The expression of circRIMS2 and BDNF in the serum of VCI patients was significantly reduced, miR-186 expression was increased, and the expression of circRIMS2 was increased in the 2VO group of mice undergoing aerobic exercise. The expression levels of circRIMS2 and BDNF in the oxygen and glucose deprivation-treated (OGD-treated) cells were decreased, the miR-186 expression and cell apoptosis were increased, while the effect was weakened after transfection with the lentiviral vector pLO-ciR-RIMS2. CircRIMS2 could bind to miR-186, and after interference with circRIMS2 in HT22 cells, the expression of miR-186 was increased. Besides, miR-186 could bind to BDNF, and BDNF expression was decreased because of the overexpression of miR-186 in HT22 cells. The expression level of BDNF in the pLO-ciR-RIMS2 group was increased, and apoptosis was decreased, but the miR-186 mimic weakened the effect of pLO-ciR-RIMS2. Aerobic exercise could shorten the average time that mice reached the platform in the Morris water maze, increase the expression level of circRIMS2 and BDNF, reduce miR-186 expression, and inhibit neuronal apoptosis. However, the interference with circRIMS2 weakened this effect. Conclusion The expression of circRIMS2 was down-regulated in VCI and aerobic exercise reduced neuronal apoptosis, and circRIMS2 improved VCI through the circRIMS2/miR-186/BDNF axis.

Objective To investigate the efficacy and safety of Tui Na for treating spasticity of the upper limbs of stroke patients. Design A prospective, multicenter, blinded, randomized controlled intervention study. Subjects Stroke patients with upper limb spasticity who were treated between December 2013 and February 2017 in 16 participating institutions in China were randomly assigned to receive either Tui Na plus conventional rehabilitation (Tui Na group, n = 222,) or conventional rehabilitation only (control group, n = 222). Methods Eligible adult patients (aged 18–75 years) were enrolled 1–12 months after stroke and randomly allocated in a 1:1 ratio to the two groups. Outcome assessors were blinded to treatment allocation. Muscle tone in the spastic muscles was evaluated using the Modified Ashworth Scale ( MAS ), and the primary endpoint was the change in MAS score over 4 weeks of treatment. Results Among patients who had experienced stroke 1–3 months before treatment, the Tui Na group experienced significantly greater reductions in MAS scores for three muscle groups than did the control group after 4 weeks of treatment. These improvements were sustained at the 3‐ and 6‐month follow‐ups. However, among patients who suffered from stroke 4–6 months and 7–12 months before treatment, the change in MAS with treatment did not differ significantly between those who did and those who did not receive Tui Na. No Tui Na‐related adverse events during treatment were reported the groups. Conclusion Tui Na was effective and safe for alleviating poststroke spasticity within 1–3 months after stroke onset.