Journal of Neurorestoratology最新文献

Background

Observational studies have reported a link between particulate matter 2.5 (PM_2.5) and the risk of mental disorders; however, the causality is unclear.

Methods

Using publicly available genome-wide association studies, we conducted a two-sample Mendelian randomization (MR) study to assess the causal relationship between PM_2.5 and six mental disorders: attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), schizophrenia (SCZ), and anxiety disorder (ANX). The inverse-variance weighting method was used as the main method for estimating causal effects. MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO were applied as supplementary analyses.

Results

Using the inverse-variance weighting method, genetically predicted PM_2.5 exposure increased the risk of ADHD (odds ratio [OR] = 1.52, 95% confidence interval [CI] = 1.16 to 1.99, p = 0.002), ANX (OR = 2.96, 95% CI = 1.29 to 6.81, p = 0.01), and SCZ (OR = 2.21, 95% CI = 1.40 to 3.47, p = 0.001). However, there was no evidence to suggest that genetically predicted exposure to PM_2.5 increased the risk of the other three mental disorders (p > 0.05).

Conclusions

The present findings enhance our understanding of the role of PM_2.5 exposure on ADHD, ANX, and SCZ risk. It may be necessary to search for novel components with neuroprotective effects to provide new preventive and therapeutic strategies for PM_2.5-induced brain damage.

Mitochondrial dysfunction is pivotal in the occurrence and development of Parkinson's disease (PD). Interventions to increase mitochondrial biogenesis and maintain the balance in mitochondrial turnover have the potential to protect against neurological damage. In addition to their crucial role in the tricarboxylic acid cycle, mitochondria impact diverse activities, including cellular metabolism, cellular quality control, and the production of reactive oxygen species. Thus, it has become imperative to better understand the regulation and function of mitochondria in PD. With this review, we aim to stimulate research that explores mitochondria-oriented neuroprotection strategies to maintain the balance in mitochondrial turnover. First, we summarize research on newly discovered genes that regulate PD mitochondrial autophagy through PTEN-induced kinase 1 (PINK1), namely AMBRA1, SYNJ2BP, and SIAH3. Second, we review PD-related mitochondrial proteins, including STRT3 and SIRT6, and the mitochondrial unfolded protein response, covering their mechanisms of involvement in PD. Third, we emphasize the roles of the mitochondrial complex, pyroptosis, and copper-induced cell death in mitochondrial damage in PD. Finally, we present a brief overview of new therapeutic strategies to correct mitochondrial defects that may be applicable for targeting mitochondria in PD patients.

Objective

Nicotinamide riboside (NR) is neuroprotective; however, its low permeability through the blood‒brain barrier restricts its therapeutic efficacy in central nervous system diseases. Compared with oral NR administration, liposome-based NR loading is hypothesized to improve its pharmacological properties during cerebral ischemia, especially when administered intravenously.

Methods

NR chloride (NRC) was encapsulated in an optimized liposome composition and administered by bolus intravenous injection. This was followed by examination of its pharmacokinetics, organ distribution, and effects on cerebral ischemia in mice.

Results

Compared with conventional NRC solution, the liposome form led to a 2.76-fold higher C_max and a 5.32-fold higher AUC_0–24h in plasma after a bolus injection of 40 mg/kg. In healthy mouse brain, it caused a significant elevation of C_max (2.93-fold) and AUC_0.25–24h (2.68-fold). In cerebral ischemia model mice, NRC liposomes increased the drug concentration at 1 and 6 h post-ischemia, increased tissue NAD⁺ and ATP levels, reduced infarct volume (by a further decrease of 35.4%), ensured neuronal survival, attenuated glial activation, and significantly improved behavioral recovery compared with conventional NRC treatment.

Conclusion

Liposome loading enhances the brain distribution and therapeutic effects of NRC, which strengthens its possibility for clinical translation and neurorestoration in stroke.

Introduction

The non-stationarity of electroencephalograms (EEG) has a substantial effect on the performance of classifiers in brain-computer interface (BCI) systems. To tackle this challenge, an adaptable version of the linear discriminant analysis (LDA) classifier was proposed. Accuracy is crucial when using BCIs for neurorestorative tasks or memory improvement. The accurate comprehension of brain responses facilitates more focused interventions, which may improve neurorestorative outcomes. BCIs equipped with adaptive classifiers are useful for personalizing therapies to individual requirements and for improving neurorestorative processes. Notably, neurorestorative interventions that yield consistent, accurate, and reliable outcomes are more likely to inspire trust and elicit satisfaction in users.

Methods

The proposed classifier continuously modified its parameters in accordance with EEG signals. The covariance matrix and mean values for each pair of classes were the updating parameters. The proposed classifier modified the model parameters by prioritizing current signal data over older signal history. The proposed classifier was tested using a hybrid SSVEP + P300 BCI system.

Results and conclusions

The proposed classifier had an estimated classification accuracy of 97.4%, and was more effective than pooled mean LDA and conventional multiclass LDA classifiers. Increased classification accuracy may increase the responsiveness of neurorestorative interventions and increase the usefulness of BCIs in neurorestoration.

Drug addiction is one of the most concerning problems globally. Significant advances have been made in understanding the physiological brain mechanisms underlying addiction to numerous substances, such as alcohol and opioids. Although experimental evidence suggests that addiction to these substances involves common neural structures and pathways, the pathophysiological mechanism underlying addiction to other substances, such as cocaine, remains uncertain. In our study, craving, as a traditional behavioral driving force of drug consumption, was revised and contrasted with alternative behavioral expressions, such as negative and positive affect, which have been shown to complement the complex expression of addictive behavior toward alcohol and other substances, for instance nicotine and opiods. In cocaine addiction, the interaction between craving behavior and the behavioral processes of positive and negative affect is unclear. Thus, we aimed to evaluate these interactions in cocaine consumers in the city of Mendoza, Argentina.

Twenty-seven men and five women were selected after providing informed consent to participate in the detoxifying program of the Psychiatric Clinic Del Prado of the city of Mendoza. Blood samples for cortisol measurement were acquired, and psychometric tests for evaluating positive and negative affect, craving, depression, and impulsivity were performed at the beginning of treatment (t₀) and at discharge on day 14 (t_F).

Results showed that negative affect and craving behavior decreased at t_F. Positive affect showed an inverse relationship with craving at t_F. Impulsivity scores improved at the end of treatment; moreover, depression and global clinical impression scores significantly improved. Cortisol blood levels significantly decreased, which suggested that patients were less stressed at t_F.

Our results suggest that during cocaine withdrawal, positive and negative affect interact with craving to reduce craving behavior, which lowers the impact of stress on consumption.

Background

Stroke is considered to be a leading cause of impairment. After experiencing strokes, patients are frequently left with impaired motor function, making it difficult to carry out daily tasks. The most extensively researched method for treating stroke patients in recent decades is CIMT (constraint-induced movement therapy), which was developed to treat upper limb deficits following stroke. CIMT entails limiting the use of the unaffected limb, altering behavior to increase the use of the affected limb, and finally, mass-training of the affected limb.

Objective

The current study aimed to determine the effectiveness of CIMT through TR for upper extremity function in stroke patients.

Materials and methods

Thirty post-stroke participants were selected on the basis of inclusion and exclusion criteria, and allocated into group A and group B. Group A was treated with CIMT in the physiotherapy department and group B was treated with CIMT through TR. Outcome measures were the Fugl-Meyer Assessment scale for upper extremities (FMA-UE), the Wolf Motor Function Test (WMFT), and the Motor Activity Log (MAL).

Results

Both groups showed significant improvements in FMA-UE, WMFT and MAL-A0U, MAL-Q0M scores. However, there were no significant differences between groups A and B in FMA-UE, WMFT, MAL-AOU, and MAL-QOM scores in the inter-group analysis.

Conclusion

CIMT via TR was equally effective than CIMT in physiotherapy department for upper extremity function in stroke. Further studies should be conducted to identify the long-term effectiveness of this approach.

Cerebrovascular disease is among the most common causes of permanent disability and mortality in adults and places immense pressure on health care resources. Metabolic diseases caused by susceptibility genes and unhealthy lifestyle play a key role in the development of cerebrovascular disease. Cardiometabolic disease is now well established and rapidly evolving. Cardiometabolic medicine, which considers metabolic issues and cardiovascular disease as an integrated whole, has been implemented in many countries worldwide. However, integrated management of metabolic risk factors and cerebrovascular disease is still in the initial stages. In this minireview, we propose a concept and definition of cerebrometabolic disease, describe its possible pathogenesis, summarize the recently proposed integrative therapeutic approach, and discuss future developments as well as challenges, with the aim of promoting a deeper understanding and integrated management of metabolic issues and cerebrovascular disease.

Background

Purinergic ligand-gated ion channel 7 receptor (P2X7R) is an ATP-gated cationic channel. It plays an important role in central nervous system diseases such as cerebral hemorrhage and Parkinson's disease, and is closely related to neuroinflammatory reactions associated with disease progression. In the present study, we evaluated the role of P2X7R in neuroinflammation and brain edema after traumatic brain injury (TBI). We also investigated the related mechanisms and potential therapeutic drugs.

Methods

In the in vivo experiments, C57BL/6 mice were randomly divided into four groups: Sham, TBI, TBI + A438079, or TBI + MCC950. The TBI model was constructed via controlled cortical impact, and mice then received saline, A438079, or MCC950 injections. Morphological damage to the brains of mice was observed by Nissl staining. Morphological and quantitative changes in microglia as well as P2X7R expression were observed via immunofluorescence. The water content of brain tissue was evaluated using the brain dry/wet weight ratio. In the in vitro experiments, lipopolysaccharides were used to stimulate murine microglial BV2 cells into an inflammatory activation state. The expression of P2X7R, interleukin (IL)-1β, IL-6, IL-12, tumor necrosis factor (TNF)-α, nuclear factor kappa-B (NF-κB), and NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasomes in BV2 cells was analyzed using enzyme-linked immunosorbent assay and Western blot. Moreover, an indirect co-culture technique was used to evaluate the effects of the neuroinflammatory model of BV2 cells on tight junction protein expression in mouse brain microvascular endothelial bEnd.3 cells.

Results

Levels of P2X7R, IL-1β, IL-6, IL-12, TNF-α, NF-κB, and NLRP3 inflammasomes were significantly higher in the TBI group than in the Sham group. TBI also increased the brain edema degree and tight junction protein expression levels. By targeting P2X7R (with A438079) or NLRP3 (with MCC950), we were able to inhibit neuroinflammation and alleviate brain edema.

Conclusions

Targeting P2X7R may help to reduce neuroinflammation and brain edema secondary to acute TBI by inhibiting the NF-κB/NLRP3 inflammasome pathway. P2X7R may be an innovative therapeutic target in TBI.