Translational Neuroscience最新文献

Background: Endovascular therapy (EVT) was the standard treatment for acute ischemic stroke with large vessel occlusion. Prognosis after EVT is always a major concern. Here, we aimed to explore a predictive model for patients after EVT.

Method: A total of 156 patients were retrospectively enrolled. The primary outcome was functional dependence (defined as a 90-day modified Rankin Scale score ≤ 2). Least absolute shrinkage and selection operator and univariate logistic regression were used to select predictive factors. Various machine learning algorithms, including multivariate logistic regression, linear discriminant analysis, support vector machine, k-nearest neighbors, and decision tree algorithms, were applied to construct prognostic models.

Result: Six predictive factors were selected, namely, age, baseline National Institute of Health Stroke Scale (NIHSS) score, Alberta Stroke Program Early CT (ASPECT) score, modified thrombolysis in cerebral infarction score, symptomatic intracerebral hemorrhage (sICH), and complications (pulmonary infection, gastrointestinal bleeding, and cardiovascular events). Based on these variables, various models were constructed and showed good discrimination. Finally, a nomogram was constructed by multivariate logistic regression and showed a good performance.

Conclusion: Our nomogram, which was composed of age, baseline NIHSS score, ASPECT score, recanalization status, sICH, and complications, showed a very good performance in predicting outcome after EVT.

Background: Due to high rates of incidence and disability, postoperative cognitive dysfunction (POCD) currently receives a lot of clinical attention. Disturbance of fatty acid oxidation is a potential pathophysiological manifestation underlying POCD. Peroxisome proliferator-activated receptor α (PPARα) is a significant transcription factor of fatty acid oxidation that facilitates the transfer of fatty acids into the mitochondria for oxidation. The potential role of PPARα intervention in POCD warrants consideration.

Objective: The present study is aimed to investigate whether PPARα agonist fenofibrate (FF) could protect long-term isoflurane anesthesia-induced POCD model and to explore the potential underlying function of fatty acid oxidation in the process.

Methods: We established the POCD model via 6 h long-term isoflurane anesthesia in vivo with C57BL/6J mice and in vitro with N2a cells. Cells and mice were pretreated with PPARα agonist FF before anesthesia, after which fatty acid oxidation and cognitive function were assessed. The level of fatty acid oxidation-related proteins was determined using western blotting. The contextual fear conditioning test was utilized to evaluate mice's learning and memory.

Results: Our results showed that 6 h long-term isoflurane anesthesia induced contextual memory damage in mice, accompanied by decreases of fatty acid oxidation-related proteins (peroxisome proliferator-activated receptor γ coactivator 1α, carnitine palmitoyltransferase 1A, and PPARα) both in the hippocampus of POCD mice and in N2a cells. In the N2a cell model, pretreatment of PPARα agonist FF led to the upregulation of fatty acid oxidation-related proteins. In vivo results showed that preconditioned FF reached similar effects. More crucially, FF has been shown to reduce cognitive damage in mice after long-term isoflurane anesthesia. Additionally, our data showed that after blocking fatty acid oxidation by Etomoxir, FF failed to protect cognitive function from long-term isoflurane anesthesia.

Conclusions: Pretreatment of PPARα agonist FF can protect against long-term isoflurane anesthesia-induced POCD by enhancing fatty acid oxidation.

Spinal cord injury (SCI) is a serious disabling injury, and the main factors causing SCI in patients include car accidents, falls from heights, as well as heavy blows and falls. These factors can all cause spinal cord compression or even complete rupture. After SCI, problems with the movement, balance, and walking ability of the lower limbs are most common, and SCI can cause abnormalities in patient's movement, sensation, and other aspects. Therefore, in the treatment of SCI, it is necessary to strengthen the rehabilitation training (RT) of patients based on data science to improve their motor ability and play a positive role in the recovery of their walking ability. This article used lower limb rehabilitation robot (LLRR) to improve the walking ability of SCI patients and applied them to SCI rehabilitation. The purpose is to improve the limb movement function of patients by imitating and assisting their limb movements, thereby achieving pain relief and muscle strength enhancement and promoting rehabilitation. The experimental results showed that the functional ambulation category (FAC) scale scores of Group A and Group B were 0.79 and 0.81, respectively, in the first 10 weeks of the experiment. After 10 weeks of the experiment, the FAC scores of Group A and Group B were 2.42 and 4.36, respectively. After the experiment, the FAC score of Group B was much higher than that of Group A, indicating that Group B was more effective in improving patients' walking ability compared to Group A. This also indicated that LLRR rehabilitation training can enhance the walking ability of SCI patients.

Objectives: Post-traumatic stress disorder (PTSD) is characterized by recurrent episodes of severe anxiety after exposure to traumatic events. It is believed that these episodes are triggered at least in part by environmental stimuli associated with the precipitating trauma through classical conditioning, termed conditioned fear. However, traditional methods of conditioned fear memory extinction are frequently ineffective for PTSD treatment due to the contribution of non-associative sensitization caused by trauma. Anesthetics have shown promise for treating various psychiatric diseases such as depression.

Methods: In this study, we examined if the inhaled anesthetic sevoflurane can suppress stress-enhanced fear learning (SEFL) in PTSD model mice. Model mice exposed to 2.4% sevoflurane for 6 h exhibited reduced freezing time and behavioral anxiety compared to sham-treated model mice. To explore the underlying mechanisms, we evaluated the regional expression levels of glucocorticoid receptors (GRs), cannabinoid CB1 receptors (CB1Rs), D1 dopamine receptors (D1Rs), and D2 dopamine receptors (D2Rs).

Results: We verified that both GR and CB1R were significantly upregulated in the hippocampus, amygdaloid nucleus, and prefrontal cortex (PFC) of model mice, while D1R and D2R were downregulated. All of these expression changes were partially normalized in the PFC by 6 h but not with 2 h sevoflurane exposure.

Conclusions: These results showed that sevoflurane exposure following traumatic events may be an effective treatment for PTSD.

Objectives: Cyclin-dependent kinase 5 (Cdk5) activity is specifically active in neurogenesis, and Cdk5 and neocortical neurons migration related biomarker are expressed in Cos-7 cells. However, the function of Cdk5 on the transformation of immortalized Cos-7 cells into neuronal-like cells is not clear.

Methods: Cdk5 kinase activity was measured by [γ-³²P] ATP and p81 phosphocellulose pads based method. The expression of neuron liker markers was evaluated by immunofluorescence, real-time PCR, Western blot, and Elisa.

Results: P35 overexpression upregulated Cdk5 kinase activity in Cos-7 cells. p35 mediated Cdk5 expression promoted the generation of nerite-like outgrowth. Compared with the empty vector, p35-induced Cdk5 activation resulted in time-dependent increase in neuron-like marker, including Tau, NF-H, NF-H&M, and TuJ1. Tau-5 and NF-M exhibited increased expression at 48 h while TuJ1 was only detectable after 96 h in p35 expressed Cos-7 cells. Additionally, the neural cell biomarkers exhibited well colocation with p35 proteins. Next-generation RNA sequence showed that p35 overexpression significantly upregulated the level of nerve growth factor (NGF). Gene set enrichment analysis showed significant enrichment of multiple neuron development pathways and increased NGF expression after p35 overexpression.

Conclusion: p35-mediated Cdk5 activation promotes the transformation of immortalized Cos-7 cells into neuronal-like cells by upregulating NGF level.

Background: Spontaneous subarachnoid hemorrhage (SAH) is the most severe form of hemorrhagic stroke and accounts for 5-7% of all strokes. Several chemical enzymes and cytokines are thought to cause reactions that may affect the mortality and morbidity of SAH patients. This study aimed to examine the possible relationships between these parameters and the occurrence of SAH and the clinical-radiological parameters in patients with acute SAH.

Methods: This study evaluated 44 patients, including 20 with SAH and 24 controls. We obtained blood from the patients and control groups, which was stored in heparinized tubes and used in determining tumor necrosis factor alpha (TNF-α), brain-derived neurotrophic factor (BDNF), acetylcholinesterase (AChE), caspase-3, and butyrylcholinesterase (BChE) enzymes.

Results: TNF-α, BDNF, AChE, and BChE enzyme levels were not related to the Glasgow Coma scale (GCS) score in the patient group (p > 0.05), whereas higher enzyme levels of caspase-3 were associated with lower GCS scores (p < 0.05). The difference between the control and patient groups in terms of mean TNF-α levels was statistically significant (p < 0.01). The BDNF levels were statistically insignificant in the patient groups (p > 0.05). Caspase-3, AChE, and BChE levels were significantly different between the control and patient groups (p < 0.01).

Conclusions: Our results may be valuable for predicting the prognosis, diagnosis, and follow-up of patients with SAH. However, further studies are required to elucidate the relationship between the clinical and radiological results in patients with SAH and certain enzymes, cytokines, and growth factors.

Increased B cell activating factor (BAFF) expression in patients with neuromyelitis optica spectrum disorder (NMOSD) is associated with B cell overstimulation, but the underlying mechanism remains unclear. This study aimed to reveal the emerging mechanisms that regulate BAFF expression in the inflammatory process of NMOSD. The results showed that the expression of miR-30b-5p was significantly decreased in NMOSD CD14⁺ monocytes compared with the normal control. Furthermore, we confirmed that metastasis-associated lung adenocarcinoma transcription 1 (MALAT1) is an upstream target of miR-30b-5p, and it could act as a ceRNA and absorb miR-30b-5p with reduced expression of miR-30b-5p. The low expression of miR-30b-5p could not bind to BAFF messenger RNA (mRNA), which resulted in the overexpression of both BAFF mRNA and protein expression. Overexpression of BAFF could bind to the corresponding receptors on B cells, which may initiate activation and proliferation of B cells and increase their production of autoantibodies. Therefore, these findings interpreted that excessive MALAT1 expression in NMOSD mononuclear macrophages led to increased BAFF expression by targeting miR-30b-5p, which caused B cell autoimmune reaction and autoantibodies production, aggravated the disease progression of NMOSD.

High concentrations of unconjugated bilirubin (UCB) have toxic effects. The aim of our study was to find a way to elevate UCB tolerance or inhibit its toxicity in neurocytes. It has been reported that cystatin C (CST3) concentrations have a significant positive correlation with total bilirubin (TB) levels and a negative correlation with albumin levels. In addition, CST3 can directly bind UCB, decrease human umbilical vein endothelial cells' permeability, improve blood-brain barrier integrity after ischemic brain injury in mice, and induce autophagy. We hypothesized that CST3 could increase the solubility of UCB, decrease permeability of neurocytes, induce autophagy of neurocytes, and alleviate bilirubin-induced damage. To verify our hypothesis, we measured TB and conjugated bilirubin levels, and the permeability and autophagy of neurocytes treated with UCB and CST3. Our findings suggest that CST3 can protect against UCB-induced damage in neurocytes and that autophagy played an important role in this process.

Prion diseases and the prion protein are only partially understood so far in many aspects. This explains the continued research on this topic, calling for an overview on the current state of knowledge. The main objective of the present review article is to provide a comprehensive up-to-date presentation of all major features of human prion diseases bridging the gap between basic research and clinical aspects. Starting with the prion protein, current insights concerning its physiological functions and the process of pathological conversion will be highlighted. Diagnostic, molecular, and clinical aspects of all human prion diseases will be discussed, including information concerning rare diseases like prion-associated amyloidoses and Huntington disease-like 1, as well as the question about a potential human threat due to the transmission of prions from prion diseases of other species such as chronic wasting disease. Finally, recent attempts to develop future therapeutic strategies will be addressed.