Translational Neuroscience最新文献

Background: Recent studies have highlighted that circular RNAs regulate cancer-related genes' expression by functioning as microRNA sponges in cancers. Herein, we investigated the function and molecular mechanism of circYIPF6 in glioma.

Methods: 5-Ethynyl-2'-deoxyuridine assay, colony formation, and flow cytometry were performed to assess the proliferation and apoptosis of glioma cells. The levels of glycolytic metabolism were evaluated by measuring the glucose uptake and lactate production. The protein levels of Bax, Bcl2, GLUT1, LDHA, and PTBP1 were examined by western blot. The interplay between miR-760 and circYIPF6 or PTBP1 was confirmed by a dual-luciferase reporter. The effect of circYIPF6 silencing on the growth of glioma in vivo was determined by a xenograft experiment.

Results: circYIPF6 was significantly upregulated in glioma. Knockdown of circYIPF6 suppressed glioma cell proliferation and glycolysis while promoting cell apoptosis. Mechanistic studies revealed that circYIPF6 targeted miR-760 and could abundantly sponge miR-760 to inhibit the expression of its downstream target gene PTBP1. Functional rescue experiments showed that both miR-760 inhibition and PTBP1 overexpression could attenuate the regulatory effect of circYIPF6 silencing on glioma cells. Furthermore, circYIPF6 knocking down effectively impeded glioma growth in vivo.

Conclusion: These findings suggested that circYIPF6 participated in the proliferation, apoptosis, and glycolysis of glioma through the miR-760/PTBP1 axis.

Background: The aim of this study was to explore the correlation between non-arteritic anterior ischemic optic neuropathy (NAION) and cerebral infarction (CI). Moreover, the ocular and systemic parameters are also compared between NAION patients with or without CI.

Methods: Retrospective analysis is performed for NAION patients and the controls. The controls were collected at the eye outpatient with cranial computed tomography (CT), and data of blood triglyceride, cholesterol, low-density lipoprotein, high-density lipoprotein, and apolipoprotein B were drawn. The diagnosed NAION patients with cranial CT are included, and data of clinical history and routine clinical examination were drawn from the medical record. Visual acuity, intraocular pressure (IOP), visual field, and visual evoked potential were also drawn.

Results: Eighty-two unilateral and 6 bilateral patients, totally 94 eyes for 88 NAION patients and 69 controls are included. NAION and control patients have matched age, gender, and weight. There is no difference in triglyceride, cholesterol, low-density lipoprotein, high-density lipoprotein, and apolipoprotein B between these two groups. NAION patients (43.18%, 38/88) have a higher ratio of CI than the controls (14.49%, 10/69) (p = 0.000). For NAION, the odds ratio (OR) of CI is 2.691 (p = 0.011). Body mass index, height, and IOP show no significant difference between NAION patients with or without CI. NAION patients with CI have a significant higher ratio of hypertension than those without CI, and the OR of HBP is 2.623 (p = 0.008).

Conclusions: The correlation between NAION and CI is possible as NAION patients have a significant higher ratio with CI. In NAION patients, hypertension is a risk factor for those with CI.

Sleep plays an important role in the learning process and memory consolidation, and sleep deprivation (SD) leads to inadequate memory consolidation and plays an important role in brain development and plasticity. SD increases β-amyloid levels while impairing cognitive function. We explored the effect of enriched environment (EE) on β-amyloid and transporter protein LRP1 and receptor for advanced glycosylation end-products (RAGE) expression in chronic sleep deprived mice. We randomly divided mice into four groups (n = 10), the standard environment group (Ctrl group), the sleep deprivation group (SD group), the enriched environment intervention group (EE group), and the sleep deprivation plus environmental enrichment intervention group (SD + EE group). A modified multi-platform SD model was used to sleep deprive the mice for 19 h per day. Five hours of EE intervention was performed daily in the EE group and the SD + EE group, respectively. The behavioral measurements of mice were performed by Y-maze method and new object recognition; the expression levels of Aβ1-42, LRP1, and RAGE in prefrontal cortex and hippocampus of mice were measured by immunofluorescence; the expression levels of LRP1 and RAGE in prefrontal cortex and hippocampus were detected by Western blot. The results showed that EE could effectively ameliorate the effects of SD on cognitive impairment, reduce SD induced Aβ deposition, and decrease the expression of RAGE, while increase the expression of LRP1.

Advanced sensors/electrodes and signal processing techniques provide powerful tools to analyze surface electromyographic signals (sEMG) and their features, to decompose sEMG into the constituent motor unit action potential trains, and to identify synergies, neural muscle drive, and EEG-sEMG coherence. However, despite thousands of articles, dozens of textbooks, tutorials, consensus papers, and European and International efforts, the translation of this knowledge into clinical activities and assessment procedures has been very slow, likely because of lack of clinical studies and competent operators in the field. Understanding and using sEMG-based hardware and software tools requires a level of knowledge of signal processing and interpretation concepts that is multidisciplinary and is not provided by most academic curricula in physiotherapy, movement sciences, neurophysiology, rehabilitation, sport, and occupational medicine. The chasm existing between the available knowledge and its clinical applications in this field is discussed as well as the need for new clinical figures. The need for updating the training of physiotherapists, neurophysiology technicians, and clinical technologists is discussed as well as the required competences of trainers and trainees. Indications and examples are suggested and provide a basis for addressing the problem. Two teaching examples are provided in the Supplementary Material.

[This retracts the article DOI: 10.1515/tnsci-2020-0128.].

Objective: This study aims to investigate the impact of vagus nerve stimulation (VNS) on the connectivity and small-world metrics of brain functional networks during seizure periods.

Methods: Ten refractory epilepsy patients underwent video encephalographic monitoring before and after VNS treatment. The 2-min electroencephalogram segment containing the ictal was selected for each participant, resulting in a total of 20 min of seizure data. The weighted phase lag index (wPLI) and small-world metrics were calculated for the whole frequency band and different frequency bands (delta, theta, alpha, beta, and gamma). Finally, the relevant metrics were statistically analyzed, and the false discovery rate was used to correct for differences after multiple comparisons.

Results: In the whole band, the wPLI was notably enhanced, and the network metrics, including degree (D), clustering coefficient (CC), and global efficiency (GE), increased, while characteristic path length (CPL) decreased (P < 0.01). In different frequency bands, the wPLI between the parieto-occipital and frontal regions was significantly strengthened in the delta and beta bands, while the wPLI within the frontal region and between the frontal and parieto-occipital regions were significantly reduced in the beta and gamma bands (P < 0.01). In the low-frequency band (<13 Hz), the small-world metrics demonstrated significantly increased CC, D, and GE, with a significantly decreased CPL, indicating a more efficient network organization. In contrast, in the gamma band, the GE decreased, and the CPL increased, suggesting a shift toward less efficient network organization.

Conclusion: VNS treatment can significantly change the wPLI and small-world metrics. These findings contribute to a deeper understanding of the impact of VNS therapy on brain networks and provide objective indicators for evaluating the efficacy of VNS.

Context: Accumulated evidence indicates that geniposide exhibits neuroprotective effects in ischemic stroke. However, the potential targets of geniposide remain unclear.

Objective: We explore the potential targets of geniposide in ischemic stroke.

Materials and methods: Adult male C57BL/6 mice were subjected to the middle cerebral artery occlusion (MCAO) model. Mice were randomly divided into five groups: Sham, MCAO, and geniposide-treated (i.p. twice daily for 3 days before MCAO) at doses of 25, 75, or 150 mg/kg. We first examined the neuroprotective effects of geniposide. Then, we further explored via biological information analysis and verified the underlying mechanism in vivo and in vitro.

Results: In the current study, geniposide had no toxicity at concentrations of up to 150 mg/kg. Compared with the MCAO group, the 150 mg/kg group of geniposide significantly (P < 0.05) improved neurological deficits, brain edema (79.00 ± 0.57% vs 82.28 ± 0.53%), and infarct volume (45.10 ± 0.24% vs 54.73 ± 2.87%) at 24 h after MCAO. Biological information analysis showed that the protective effect was closely related to the inflammatory response. Geniposide suppressed interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) expression in the brain homogenate, as measured by enzyme-linked immunosorbent assay (ELISA). Geniposide upregulated A20 and downregulated TNF receptor-associated factor-6 and nuclear factor kappa-B phosphorylation in the MCAO model and lipopolysaccharide-treated BV2 cells at 100 μM.

Conclusions: Geniposide exhibited a neuroprotective effect via attenuating inflammatory response, as indicated by biological information analysis, in vivo and in vitro experiments, which may provide a potential direction for the application of geniposide in the treatment of ischemic stroke.

Objective: This research was conducted to discuss the recent prognosis of patients with acute cerebral infarction (ACI) combined with cerebral-cardiac syndrome (CCS).

Method: Eighty-seven patients with ACI were selected, which were divided into the ACI group (52 patients) and the CCS group (35 patients) according to whether the CCS was combined, and another 30 health controls were selected as the control group. Serum hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) levels of subjects in each group at the 1st day, the 3rd day, and the 7th day after admission were measured by enzyme-linked immunosorbent assay. After discharge for 30 days, the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) score were utilized to evaluate the prognosis of patients. The role of serum HIF-1α and VEGF levels in the prognosis of ACI combined with CCS patients was assessed by receiver operating characteristic curve and the binary logistic regression analysis.

Results: Higher serum HIF-1α and VEGF levels were observed in the CCS and ACI groups versus the control group, and the levels of which were even higher in the CCS group in comparison to the ACI group. According to the prognosis of the NIHSS score, fasting blood glucose (FBG), Acute Physiology and Chronic Health Evaluation II score, creatine kinase-MB (CK-MB), and HIF-1α and VEGF levels at the 7th day of admission were higher while Glasgow coma scale (GCS) score was lower in the poor prognosis group than those in the good prognosis group, and the area under the curve (AUC) of serum HIF-1α and VEGF levels was 0.895 (95% confident interval [CI], 0.786-1.000), and 0.855 (95% CI, 0.731-0.980). According to the prognosis of the mRS score, FBG, CK-MB, and HIF-1α and VEGF levels at the 7th day of admission were higher while GCS score was lower in the poor prognosis group than those in the good prognosis group, and the AUC of serum HIF-1α and VEGF levels was 0.850 (95% CI, 0.722-0.979) and 0.901 (95% CI, 0.798-1.000). The results of the binary logistic regression analysis revealed that HIF-1α and VEGF levels may be independent risk factors influencing the prognosis of ACI combined with CCS.

Conclusion: Serum HIF-1α and VEGF have a good predictive value for assessing the recent prognosis of patients with ACI combined with CCS, which could be independent risk factors influencing the prognosis of disease.

Background: The role of the willisian collaterals during carotid endarterectomies (CEAs) is a debated issue. The aim of the present work was to test whether an incomplete or non-functional circle of Willis (CoW) is a risk factor for ischemic events during CEA.

Patients and methods: CEAs were performed under local anesthesia. Patients were considered symptomatic (SY) if neurological signs appeared after the cross-clamping phase. In SY patients shunt insertion was performed. CoW on CT angiograms (CTa) were analyzed offline and categorized as non-functional (missing or hypoplastic collaterals) or functional collaterals by three neuroradiologists. Near-infrared spectroscopy (NIRS) was performed throughout the procedure.

Results: Based on CTa, 67 incomplete circles were found, 54 were asymptomatic (ASY) and 13 were SY. No complete CoW was found among the SY patients. Significant differences could be detected between incomplete and complete circles between ASY and SY groups (Chi-square: 6.08; p = 0.013). The anterior communicating artery was missing or hypoplastic in 5/13 SY cases. There were no cases of the non-functional anterior communicating arteries in the ASY group (Chi-square: 32.9; p = 10^-8). A missing or non-functional bilateral posterior communicating artery was observed in 9/13 SY and in 9/81 ASY patients (Chi-square: 24.4; p = 10^-7). NIRS had a sensitivity of 76.9% and a specificity of 74.5% in detecting neurological symptoms.

Conclusions: Collateral ability of the CoW may be a risk factor for ischemic events during CEAs. Further studies should delineate whether the preoperative assessment of collateral capacity may be useful in decision-making about shunt use during CEA.

Objective: MiRNAs play a key role in ischemic stroke (IS). Although miR-101-3p can participate in multiple disease processes, its role and mechanism in IS are not clear. The aim of the present study was to observe the effect of miR-101-3p activation on IS in young mice and the role of HDAC9 in this effect.

Methods: The young mice were first subjected to transient middle cerebral artery occlusion (tMCAO) or sham surgery, and the cerebral infarct area was assessed with 2,3,5-triphenyltetrazolium chloride staining. Meanwhile, the expressions of miR-101-3p and HDAC9 were tested using RT-qPCR or western blot. Besides, neuron morphology and apoptosis were confirmed using Nissl staining and TUNEL staining.

Results: We first verified that miR-101-3p was downregulated and HDAC9 was upregulated in the brain tissue of tMCAO young mice. Moreover, we proved that overexpression of miR-101-3p could improve cerebral infarction, neuronal morphology, and neuronal apoptosis in tMCAO young mice by lowering the expression of HDAC9.

Conclusions: Activation of miR-101-3p can protect against IS in young mice, and its mechanism is relevant to the inhibition of HDAC9. Therefore, miR-101-3p and HDAC9 might be the latent targets for IS therapy.