Journal of Neurorestoratology最新文献

Background

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Despite its biological underpinnings, ASD is yet diagnosed based on behavioral assessments. The importance of early ASD detection is supported by a large body of evidence. Early diagnosis can facilitate more effective interventions, reducing the socioeconomic costs and improving the quality of life of both children with ASD and their families. This study aims to investigate the expression patterns of ASD-related microRNAs (miRNAs) in Iranian children with ASD compared with matched neurotypical controls, to identify candidate miRNA biomarkers.

Method

Validation of ASD-related miRNAs was performed using the qRT-PCR method in plasma samples from 20 ASD and 20 unaffected individuals. Differentially expressed miRNAs were identified based on relative quantification analysis. Then, the diagnostic potential of each candidate miRNA was assessed using receiver operating characteristics (ROC) curve analysis.

Results

Based on statistical and bioinformatics analyses, eight miRNAs were recommended as candidate biomarkers. Furthermore, differential expression of five of these miRNAs—miR-146a-5p, miR-338-3p, miR-181b-5p, let-7a-5p, and miR-140-3p—was confirmed experimentally by qRT-PCR (p-value < 0.05) based on a t-test. miR-140-3p was not further detected as significant by the Mann–Whitney test. The sensitivity, specificity, and area under the ROC curve were calculated for each validated miRNA and fell in the ranges of 75%–91%, 66.67%–83.33%, and 74%–90%, respectively.

Conclusions

This study revealed a panel of high-confidence differentially expressed miRNAs, which requires further investigation in larger sample sizes and by other validation tests. These findings could be a step forward in the field of ASD biomarker discovery.

Introduction

Functional connectivity across large-scale networks is crucial for the regulation of conscious states. Nonetheless, our understanding of potential alterations in the temporal dynamics of dynamic functional connectivity (dFC) among patients with disorders of consciousness (DOC) remains limited. The present study aimed to examine different time-scale spatiotemporal dynamics of electroencephalogram oscillation amplitudes recorded in different consciousness states.

Methods

Resting-state electroencephalograms were collected from a cohort of 90 patients with DOC. The sliding window approach was used to create dFC matrices, which were subsequently subjected to k-means clustering to identify distinct states. Finally, we performed state analysis and developed a decoding model to predict consciousness.

Results

There was significantly lower dFC within the forebrain network in patients with unresponsive wakefulness syndrome than in those with a minimally conscious state. Moreover, there were significant differences in temporal properties, mean dwell time, and the number of transitions in the high-frequency band at different time scales between the unresponsive wakefulness syndrome and minimally conscious state groups. Using the multi-band and multi-range temporal dynamics of dFC approach, satisfactory classification accuracy (approximately 83.3 %) was achieved.

Conclusion

Loss of consciousness is accompanied by an imbalance of complex dynamics within the brain. Both transitions between states at short and medium time scales in high-frequency bands and the forebrain are important in consciousness recovery. Together, our findings contribute to a better understanding of brain network alterations in patients with DOC.

Magnesium is an essential nutrient involved in a wide range of physiological activities to maintain normal brain functions. So far, magnesium has been recognized as a cofactor for over 600 enzymatic reactions within the body. Importantly, magnesium deficiency has been implicated in the pathogenesis of various dementia-related diseases containing cardiovascular diseases and Alzheimer’s disease (AD). With increased aging, the incidence and prevalence of dementia are expected to rise dramatically double every 20 years worldwide. Accumulating evidence indicates that dementia-related diseases are associated with low magnesium levels, and dietary magnesium intake can improve cognitive function. Many studies have revealed that magnesium ions act as a natural Ca²⁺ blocker to inhibit calcium overload and halt the course of AD by blocking N-methyl-D-aspartate receptors and thus inhibiting neuronal overactivation. In addition, magnesium ions can inhibit glial cell-mediated neuroinflammation by down-regulating pro-inflammatory cytokines and oxidative stress, which have been implicated in the development of chronic age-related diseases. Thus, magnesium may be a target for the prevention and treatment of neurological diseases. Taken together, maintaining an optimal magnesium balance may help in the prevention of cognitive decline and dementia. In this review, we summarize our current understanding of the role of magnesium in dementia, highlighting recent progresses in the field.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a relatively common inherited arterial smooth muscle cell disease. The genetic defect is localized to the notch homolog protein 3 (NOTCH3) gene on chromosome 19q12 and is due to a missense variant in NOTCH3. The main clinical manifestations are transient ischemic attacks and repeated stroke, with cognitive impairments leading to dementia, migraine with aura, and mental/emotional disorders. To date, there is no specific therapeutic option, with only symptomatic supportive treatment for the symptoms of acute stroke, migraine, dementia, and mental abnormalities. Here, we provide a case report of a Chinese patient with CADASIL and a mutation in exon 4 of the NOTCH3 gene (p.Arg133Cys). The patient mainly exhibited recurrent cerebral infarction and affective disorder. Antidepressant treatment combined with repetitive transcranial magnetic stimulation significantly improved the depressive symptoms of the patient.

Objective

To retrospectively analyze the distribution characteristics of pathogenic bacteria in the cerebrospinal fluid (CSF) of patients with severe intracranial infection after craniotomy and treatment results. The aim was to provide a clinical basis and reference for improving treatment for severe intracranial infections.

Methods

This was a retrospective analysis of the distribution of pathogenic bacteria and the therapeutic effect for 43 patients who developed severe intracranial infections after craniotomy. All patients had positive CSF cultures and were treated in two hospitals in Beijing from May 2015 to May 2020. All patients received an intravenous injection of sensitive antibiotics combined with a CSF lateral ventricle catheter or lumbar cistern drainage. Antibiotic lavage treatment was administered through an external drain.

Results

The CSF bacterial culture results for the 43 patients showed 34 single-strain infections (26 Gram-positive bacteria and 8 Gram-negative bacteria) and 9 multistrain infections. Fifty-two pathogenic strains were isolated, namely 32 Gram-positive bacteria (61.54%), 18 Gram-negative bacteria (34.61%), and 2 fungi (3.85%). After combined treatment, 29 patients (67.44%) were cured; treatment was effective for 7 patients (16.28%) and ineffective for 7 patients (16.28%). After 6 months of follow-up, the 36 surviving patients were cured of infection. The Glasgow Outcome Scale score results showed that 5 of the 36 (13.9%) patients had a persistent vegetative state; 13 (36.1%) had severe disability; 12 (33.3%) had moderate disability; and 6 (16.7%) had mild disability.

Conclusion

CSF pathogenic bacteria in patients with intracranial infection after craniotomy were mainly Gram-positive bacteria, primarily Staphylococcus epidermidis. A small number of patients had mixed bacterial infections. Owing to the presence of implanted devices in patients who underwent ventriculoperitoneal shunt surgery, the antibacterial therapeutic effect was worse than that for other types of postoperative infections. Therefore, when initial intravenous antibiotics are ineffective, the shunt device should be removed or replaced as soon as possible. When initial intravenous antibiotics are ineffective and severe intracranial infection occurs, a combined treatment plan should be adopted. That is, CSF drainage and antibiotic lavage should be performed cautiously with the intravenous injection of sensitive antibiotics. Our clinical data confirmed that postoperative neurosurgical infection could lead to different degrees of nerve dysfunction, which should be considered.

Background

Ischemic stroke is characterized by high incidence, high disability rate, and high recurrence rate. Stroke recurrence is a complex pathological phenomenon involving multiple factors. Logistic regression analysis is widely used in traditional medical statistical analysis. However, this method mainly investigates the net effect of single factors using large sample sizes. The fsQCA method is a more suitable means of analyzing the configuration effect of risk factors affecting cerebral infarction recurrence, because it is based on holism and considers interaction effects among the risk factors.

Objective

The purpose of this study was to explore the risk factors of cerebral infarction recurrence using fsQCA, to reveal the configurations that resulted in cerebral infarction recurrence, and to provide novel ideas for the prevention of recurrence.

Methods

A total of 155 cerebral infarction patients admitted to the Department of Neurology of a tertiary class hospital in Shandong province from June 2020 to June 2021 were selected to participate. The demographic characteristics and risk factors associated with recurrence of cerebral infarction were collected, and participants were followed for one year.

Results

The comparative analysis was performed by fuzzy-set (fsQCA 3.0) software. We conducted a configuration analysis of the risk factors of cerebral infarction recurrence and generated eight different configurations by analyzing various combinations of eight risk factors.

Conclusion

This study presented results different from those reported in studies using linear regression models. It took into consideration the configurational effect of each conditional variable on cerebral infarction recurrence. To prevent such recurrences, medical workers should evaluate the combination of multiple influencing factors, instead of focusing on a single factor.

Background

Drug-resistant epilepsy (DRE) affects more than 20 million people worldwide. DRE patients do not respond to anti-seizure medications. Shifting from anti-seizure to anti-epileptic and disease-modifying therapy will be an important aim for future research. The canonical nuclear factor kappa B (NF-κB) signaling pathway plays a pivotal role in epilepsy and neuroinflammation. However, the expression and regulation of RelB, which can be activated via both canonical and non-canonical NF-κB signaling, are obscure in epilepsy. To clarify the expression and localization of RelB in the DRE phenotype and to determine the proteins related to RelB regulation, we conducted the following studies.

Methods

Quantitative PCR was performed to detect the transcription of RELB in pilocarpine-induced epileptic rats. Western blotting was used to determine the abundance of RelB and proteins related to RelB regulation in brain tissue from both epilepsy model rats and DRE patients and in liposaccharide-induced HT22 cells. Immunofluorescence staining and immunohistochemistry were used to locate RelB in brain sections from DRE patients. ELISA was used to determine inflammatory cytokines secreted by HT22 cells into the culture medium.

Results

RELB transcription and expression were increased in the hippocampus and cortex of epileptic rats during the acute and latent phases and in epileptic foci of patients with temporal lobe epilepsy. Additionally, RelB levels were mainly increased in epileptic rat neurons and accumulated in the nuclei of hippocampal neurons. Further research demonstrated increased GSK3β phosphorylation at the Ser9 inhibitory site and decreased IκBα levels, which contributed to RelB accumulation in hippocampal neurons after seizure and in liposaccharide-stimulated HT22 cells.

Conclusions

This study is the first to demonstrate that RelB is widely distributed and increased in epileptogenic foci neurons in epileptic phenotypes. These results indicate that RelB may play roles in DRE and is mediated by GSK3β and IκBα, providing a new target for anti-epileptic and disease-modifying therapy.

Background

Spinal cord injury (SCI) is a devastating disease with no clear molecular mechanisms or effective treatments. Murine models of SCI have been widely used to explore its pathogenesis.

Methods

In this study, a comprehensive bioinformatic analysis using GEO datasets was performed to evaluate the characteristics of different SCI models.

Results

We found that the contusion model was similar to the compression model, with inflammation and apoptosis significantly enriched, while more complex biological processes existed in hemisection and transection model. Inflammatory markers can be used as a primary evaluation index of SCI models not only in the acute and subacute phases, but also in the chronic phase. In the meantime, apoptosis markers are more suitable for evaluating mouse SCI models while inflammatory markers are more suitable for rat SCI models. In addition, SCI models with different ages, genders, injury positions, and injury levels were also analyzed.

Conclusion

Our findings indicate that SCI is a heterogeneous disease and play an instructive role in model selecting.

Objective

This study aims to investigate the role of apoptosis and autophagy under endoplasmic reticulum (ER) stress in a lithium-treated SCI model.

Methods

We established a rat thoracic 10 (T10) spinal cord contusion model and observed its therapeutic effect by intraperitoneal (IP) injection of lithium. Histological and behavioral recovery with or without lithium injection were evaluated after rat spinal cord injury. In addition, we employed an oxygen-glucose deprivation (OGD)-PC12 cell model to study the effects of lithium on OGD-PC12 cell apoptosis, autophagy and ER stress.

Results

We found that lithium administration to SCI rats reduced neuronal apoptosis and autophagy, restored rat locomotor function by reducing ER stress via IRE1 and PERK/eIF2α pathways. In vitro experiments confirmed that upon lithium treatment, OGD-PC12 cells resisted ER stress caused by thapsigargin (TG) via the IRE1 and PERK/eIF2α signaling pathways.

Conclusion

Lithium attenuated neuronal apoptosis and autophagy, and facilitates the recovery after spinal cord injury through ameliorating ER stress, providing a new therapeutic mechanism for lithium to treat SCI.

In individuals with ventilatory pump failure (VPF) prophylactic, mechanically assisted airway clearance (ACT) by means of Mechanical Insufflation Exsufflation (MIE), is an important mitigation strategy to prevent respiratory infection, decompensation, and ultimately acute respiratory failure (ARF). VPF secondary to respiratory muscle dysfunction is a significant risk factor in neuromuscular disorders, spinal cord injury, chest wall disease, and may occur in some instances of morbid obesity. In the intensive care unit (ICU), MIE has been shown to help avoid the need for tracheostomy tube placement and improve the success rate of extubation from mechanical ventilation, especially when MIE is used in combination with continuous noninvasive ventilatory support (CNVS). Globally, clinicians are recognizing that initial titration of the settings and ongoing management of MIE can be guided by the flow and pressure waveforms that are a feature of at least one widely available MIE device.