Translational Neuroscience最新文献

Objective: Parkinson's disease (PD) is the second most common neurodegenerative disease with complex pathogenesis. Although HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1) is upregulated in PD, its exact role in HOTAIRM1 is seldom reported. The purpose of this study is to research the effect of HOTAIRM1 on 1-methyl-4-phenylpyridonium (MPP⁺)-induced cytotoxicity and oxidative stress in SH-SY5Y cells.

Methods: SH-SY5Y cells were treated with MPP⁺ at various concentrations or time points to induce SH-SY5Y cytotoxicity, so as to determine the optimal MPP⁺ concentration and time point. HOTAIRM1 expression upon MPP⁺ treatment was analyzed through qRT-PCR. Next, HOTAIRM1 was downregulated to observe the variance of SH-SY5Y cell viability, apoptosis, oxidative stress-related indexes, and protein levels of the Nrf2/HO-1 pathway. In addition, rescue experiments were carried out to assess the role of Nrf2 silencing in HOTAIRM1 knockdown on MPP⁺-induced oxidative stress in SH-SY5Y cells.

Results: MPP⁺ treatment-induced cytotoxicity and upregulated HOTAIRM1 expression in SH-SY5Y cells in a dose- and time-dependent manner. Mechanically, HOTAIRM1 knockdown enhanced cell viability, limited apoptosis, and oxidative stress, therefore protecting SH-SY5Y cells from MPP⁺-induced SH-SY5Y cytotoxicity. On the other hand, HOTAIRM1 knockdown activated the protein levels of Nrf2 and HO-1. Nrf2 silencing could counteract the neuroprotective effect of HOTAIRM1 knockdown on in vitro PD model.

Conclusion: Our data demonstrated that HOTAIRM1 knockdown could inhibit apoptosis and oxidative stress and activated the Nrf2/HO-1 pathway, therefore exerting neuroprotective effect on the PD cell model.

Background: Stroke patients often show postural instability. The patellar tendon reflex is a basic physical examination for stroke patients. This study aimed to explore the correlation between patellar tendon reflex grade and postural stability among stroke patients.

Methods: A total of 37 elderly stroke patients, each with the same quadriceps muscle strength but different patellar tendon reflex levels, were tested on a force platform under eyes-open (EO) and eyes-closed (EC) conditions. Parametric analysis, detrended fluctuation analysis (DFA), and power spectral density (PSD) analysis were used in centre of pressure (COP) signal processing. The correlation between the results of measured data processing and the level of patellar tendon reflex was analysed.

Results: All three parameters of COP (the length of the sway trajectory, the mean range of the sway trajectory in the mediolateral [ML] direction [R _x ], and the mean range of the sway trajectory in the anterior-posterior [AP] directions [R _y ]) were negatively correlated with the patient's patellar tendon reflex grade under the EC condition. The DFA results showed that a higher grade of patellar tendon reflex was associated with a smaller value of the crossover point in the AP direction. Only the PSD values of each frequency band in the AP direction were negatively correlated with patellar tendon reflex grade with EO and became negatively correlated in both AP and ML directions with EC. Overall, the results showed a strong correlation between patellar tendon reflex and postural stability in stroke patients when vision was blocked.

Significance: The strong correlation with EC may provide insights into clinic evaluation and treatment for rehabilitation or fall risks of stroke patients.

Objective: We studied whether enriched environment (EE), a classic epigenetics paradigm, can prevent cellular plasticity damage caused by chronic sleep deprivation (SD).

Methods: We performed SD in mice by a modified multi-platform method (MMPM). Mice in the SD group were deprived of sleep for 18 h a day. In addition, half of the mice in the chronic SD group were exposed to EE stimuli for 6 h per day. Immunostaining analyzed neurogenesis and neural progenitor cell-differentiated phenotypes in the hippocampal dentate gyrus (DG) region.

Result: At 13 weeks, compared with the control group, SD severely impaired the proliferation and differentiation of neural stem cells, and EE completely reversed the process. SD can induce gliosis in the mouse hippocampus, and EE can delay the process.

Conclusion: Our results suggest that chronic SD may damage the neurogenesis in the DG of the hippocampus. However, enrichment stimulation can reverse the processing by promoting neuronal repair related to neuronal plasticity.

Objective: Anesthetic exposure causes learning and memory impairment, the mechanisms of which remain unknown. It has been reported that tumor necrosis factor-α-inducer protein 8-like 2 (TIPE2) is a newly discovered immune negative regulator that is essential for maintaining immune homeostasis. This study aimed to examine the role of TIPE2 in isoflurane-induced postoperative cognitive decline (POCD).

Methods: An AAV empty vector and AAV shTIPE2 vector for the knockdown of TIPE2 were injected into the dorsal hippocampus of mice. Mice were continuously exposed to 1.5% isoflurane followed by abdominal exploration. Behavioral tests including the open field test and fear conditioning test were performed on the third and fourth day post-operation. Apoptosis was detected by terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling staining. The kits were used to detect the activity of antioxidant enzymes. Inflammatory cytokine levels were detected by enzyme-linked immunosorbent assay. Signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB) signaling pathway activities were detected by western blotting.

Results: TIPE2 expression increased after isoflurane anesthesia and surgery. TIPE2 deficiency aggravated cognitive impairment in mice and further caused apoptosis and oxidative stress in hippocampal neurons. TIPE2 deficiency induced microglial activation and increased secretion of proinflammatory cytokines. In addition, TIPE2 deficiency promoted STAT3 and NF-κB signaling activation induced by isoflurane anesthesia and after surgery.

Conclusion: TIPE2 may play a neuroprotective role in POCD by regulating STAT3 and NF-κB pathways.

Objective: Thoracic surgery is easy to cause various perioperative complications, especially in elderly patients, due to their physical weakness and physiological function degeneration. Postoperative cognitive dysfunction is a common complication in elderly patients undergoing thoracic surgery. This study focuses on exploring the effects of thoracic paravertebral block (TPVB) combined with general anesthesia on postoperative functional recovery in elderly patients undergoing thoracoscopic radical resection for lung cancer based on enhanced recovery after surgery (ERAS) pathway.

Methods: A total of 104 patients aged 60 years or older undergoing thoracoscopic radical resection of lung cancer were randomized into the combination group (n = 52) and the control group (n = 52). Patients in the control group were given general anesthesia alone, while patients in the combination group were given TPVB combined with general anesthesia. All patients applied the ERAS model for the perioperative intervention. Hemodynamic indices (heart rate [HR] and mean arterial pressure [MAP]) before anesthesia (T0), 5 min after thoracoscopic trocar placement (T1), at extubation (T2), 30 min after extubation (T3), and 6 h after the surgery (T4), postoperative analgesia, preoperative and postoperative serum pain stress factors (5-hydroxytryptamine [5-HT], prostaglandin E2 [PGE2], cortisol [Cor], substance P [SP], and norepinephrine [NE]), tumor markers (CYFRA21-1, CEA, and CA50), inflammatory factors (IL-6, TNF-α, and c-reactive protein (CRP)), lung function indicators (forced vital capacity [FVC] and forced expiratory volume in the first second [FEV1]), 6 min walking distance (6MWD), clinical recovery indicators, hospitalization status, and postoperative complications in patients between both groups were compared.

Results: Compared with the control group, patients in the combination group had lower HR and MAP at T1-T4 time points, less intraoperative doses of remifentanil and propofol, less patient-controlled interscalene analgesia compression number 24 h after the surgery, lower visual analogue scale scores 24 h after the surgery, shorter hospitalization time, postoperative off-bed time, postoperative chest tube removal time, postoperative first feeding time and gastrointestinal function recovery time, reduced postoperative serum levels of 5-HT, PGE2, Cor, SP, NE, CYFRA21-1, CEA, CA50, IL-6, TNF-α, and CRP, decreased complications, and higher FVC, FEV1, and 6MWD.

Conclusion: Based on the ERAS pathway, TPVB combined with general anesthesia in thoracoscopic surgery for lung cancer in elderly patients can effectively reduce the patients' hemodynamic fluctuations, alleviate postoperative pain, accelerate the recovery process, and reduce complications.

Sepsis is a potentially fatal organ failure resulting from a dysregulated host response to infection. It can be a substantial financial burden on families and society due to the high cost of medical care. The study aims to investigate the protective roles of Esmolol in mice with sepsis-induced brain injuries against cognitive dysfunction and neuronal inflammation. Male C57BL/6J mice were intraperitoneally injected with LPS (10 mg/kg, L2630, Sigma) to establish a septic encephalopathy model. Esmolol (15 mg/kg/h, HY-B1392, MedChemExpress) was subcutaneously infused using osmotic mini-pumps for 6 h before LPS injection. Morris water maze and novel object recognition tests evaluated LPS-induced cognitive impairment and behavioral phenotypes. Cytokines and protein expression were assessed using ELISA assay and RT-qPCR. Esmolol treatment potentially improved cognitive impairment in septic mice. Esmolol administration markedly diminished the abnormal hippocampal neuronal structure, and the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α was significantly downregulated in the hippocampal tissue. Esmolol treatment significantly reduced apoptotic TUNEL-positive cells and reversed the related gene expression (BAX and BCL-2). The effects of esmolol on the reactive oxidative species and oxidative stress markedly reduce malondialdehyde MDA content and increase superoxide dismutase and catalase in hippocampal tissues. In addition, esmolol significantly reduced the percentage and density of Iba-1 + microglia in septic mice. Our results demonstrated that esmolol potentially improved cognitive impairment and neuronal inflammation in mice with sepsis-induced brain injury.

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.

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.

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

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.