Journal of Neurorestoratology最新文献

Background

C-type natriuretic peptide (CNP) can be altered during stress and has protective effects in both the heart and brain; the functions of both organs can be positively affected by CNP modulation. Low arousal sounds can modulate heart–brain communication and improve stress responses. Here, we aimed to explore the modulation of CNP and glial fibrillary acidic protein (GFAP) and neuroprotective effects of low arousal theta frequency sound (TFS).

Methods

Chronic stress was induced in mice (n > 4) using four different stressors on alternate days for 15 days, followed by TFS therapy on alternate days. Open field and elevated plus maze tests were administered for the behavioral analysis, and enzyme-linked immunosorbent assay was used to analyze corticosterone, dopamine, and serotonin levels. Hematoxylin and eosin and cresyl violet staining were used for the morphological analysis of brain and heart sections, and immunohistochemistry for GFAP and CNP was performed.

Results

TFS significantly increased the time spent in the open arms during the elevated plus maze (p < 0.05) and improved exploration in the open field test (p < 0.05). In both tests, decision-making times were significantly reduced by TFS. Nuclear morphology and GFAP expression demonstrated significantly reduced gliosis in fear pathways after TFS therapy x. CNP levels were restored in fear pathways but not intrinsic cardiac ganglia (responsible for heart–brain communication) in TFS-treated mice. Brain corticosterone and dopamine levels increased after TFS therapy, reflecting restored motivational behaviors.

Conclusions

Low arousal TFS is a potential neuromodulator for treating stress and related complications.

STXBP1 encephalopathy (STXBP1-E) is a rare neurodevelopmental disorder that includes epilepsy; it is caused by de novo STXBP1 mutations. In clinical settings, pharmaceutical interventions to treat STXBP1-E predominantly concentrate on seizure control. However, effective treatments for seizure recurrence, treatment resistance, and common comorbidities remain scarce. Patients with STXBP1-E display a wide range of pathogenic variations that manifest as loss-of-function, gain-of-function, or dominant-negative effects. However, recent studies have primarily investigated the pathogenic mechanisms resulting from loss-of-function mutations using STXBP1 haploinsufficiency models. This approach fails to accurately assess the impact of disease-causing mutations. Moreover, to evaluate new syntaxin-binding protein 1 (STXBP1)-targeting drugs, novel models that incorporate disease-causing mutations or even the genetic backgrounds of patients are needed. Here, we discuss the clinical symptoms of STXBP1-E and the relationship between this disorder and STXBP1 mutations. We also review recent progress toward understanding the biological function of STXBP1 and its deficiency-induced cellular defects. We then discuss recent discoveries concerning the pathogenesis of STXBP1-E and the limitations and challenges associated with the current research model. Additionally, we underscore the value of leveraging stem cell technology to study the pathogenic mechanisms of STXBP1-E, and review stem cell transplantation as a potential approach for treating this disorder. We also discuss potential future research directions that need to be resolved.

Background

Ultrashort wave (USW) therapy has been reported to alleviate cerebral ischemia/reperfusion (IR) injury, however the underlying mechanisms remain elusive. The aim of this study was to observe the effect of non-thermal USW therapy on neuronal damage and expression of heat shock protein 70 (HSP70) after cerebral IR in rats.

Methods

Focal ischemia-reperfusion (IR) was induced in Sprague–Dawley rats by middle cerebral artery occlusion/reperfusion (MCAO/R). The Ninety-two rats (both male and female) were screened using the Zea-Longa 5 grade evaluation. Included rats were then randomly divided into blank, sham, model 1-day, model 3-day, model 7-day, USW 1-day, USW 3-day, or USW 7-day groups. All rats in the model groups received sham USW treatment, while rats in the USW groups received USW treatment, for 1, 3, or 7 days. We assessed the National Institutes of Health Stroke Scale, brain infarction volumes, ultrastructural damage scores using electron microscopy, and HSP70 expression by western blotting between the different groups.

Results

USW treatment reduced the National Institutes of Health Stroke Scale, infarction volume, and ultrastructural neuronal damage, and increased expression of HSP70, in the hippocampal CA1 region.

Conclusions

Non-thermal USW therapy may improve neurological function, decrease infarction volume, and reduce neuronal damage by increasing HSP70 expression following cerebral IR injury.

Depression is a mental disease that involves a variety of complex physiological mechanisms. A wide range of methods have therefore been used to establish mouse models of depression, and there are currently many ways to develop such mouse models. The present study aimed to compare the effects of various model induction methods and assesses their different effects. To this end, C57BL/6J mice were divided into three experimental groups: the chronic restraint stress (CRS) group received 6 hours of daily confinement within restraint tubes over a 3-week period; the chronic lipopolysaccharide (C-LPS) administration group received daily intraperitoneal injections of 0.5 mg/kg LPS for 1 week; and the acute LPS (A-LPS) administration group received a singular intraperitoneal injection of 0.83 mg/kg LPS. A corresponding control group was established for each experimental condition. Following mouse model establishment, depression-like behaviors were assessed through the forced swimming and tail suspension tests; anxiety-related behaviors were evaluated using the open field test and elevated plus maze. Furthermore, the expression of the immediate early gene c-Fos, ionized calcium-binding adapter molecule 1 (IBA1), and glial fibrillary acidic protein (GFAP) was examined via immunofluorescence. Longer immobility durations during the forced swimming and tail suspension tests were observed across all model groups (p < 0.05), indicating depression-like behaviors. Furthermore, the CRS and C-LPS group, but not the A-LPS group, showed significant anxiety-like behaviors in the elevated plus maze (p < 0.05). All model groups also exhibited significant increases in both time and distance explored within the central area of the open field test (p < 0.05). The activation of GFAP- and IBA1-positive cells in the cerebral cortex and hippocampus was also markedly pronounced in all experimental groups, suggesting the association of neuroinflammatory responses with induced depressive states. The present findings contribute to our understanding of the pathophysiology of stress-induced and neuroinflammatory-associated depression, and will help researchers to choose suitable depression models for their investigations.

Restoring function to peripheral nerves with a gap is challenging, with <50% of patients undergoing nerve repair surgery recovering function. Sensory nerve grafts (autografts) are the clinical “gold standard” for bridging nerve gaps to restore sensory and motor function. They have significant limitations and restore meaningful function only across short gaps when repairs are performed soon after trauma and patients are young. When the value of any of these variables is large, the extent of recovery decreases precipitously, and when two or all are simultaneously large, there is little to no recovery. The extent of restored meaningful recovery has not increased in almost 70 years. Thus, novel techniques are needed that enhance both the extent of recovery and the percentage of patients who recover meaningful recovery. This paper reviews the limitations of autografts and other materials used to repair nerves. It also examines autologous platelet-rich plasma (PRP), a promising nerve gap repair technique that induces recovery in clinical settings where autografts are ineffective, including when the values of all three variables are simultaneously large.

Stroke is a global cause of death and neurological disability. Survivors of stroke experience impaired quality of life because of post-stroke motor disorders, which are the primary driver of stroke-associated healthcare expenditures. Neuromodulatory techniques offer a promising avenue for addressing these post-stroke motor disorders. Post-stroke motor disorders are thought to be related to ongoing maladaptive responses and abnormal brain network reorganization; this offers insights into the inadequacy of most current treatments. In the present review, we summarize the following models involved in post-stroke motor disorders: the dual-pathway model of the basal ganglia, the cerebrocerebellar model, and the interhemispheric inhibition model. By identifying these critical elements, it will be clinically possible to explore mechanism-based therapeutics. On the basis of this physiological understanding, we review progress in the clinical application of the main therapeutic modalities; namely, invasive deep brain stimulation (DBS) and noninvasive transcranial magnetic stimulation (TMS), both of which are currently under investigation for neuromodulation in stroke. Both DBS and TMS are approved by the Food and Drug Administration because of their safety and efficacy. Although little is known about their underlying molecular mechanisms, recent studies have indicated that DBS and TMS promote post-stroke neurogenesis and neuroplasticity, suggesting potential pathways for restoring post-stroke motor disorders. Moreover, we focus specifically on the interactions between TMS and DBS, and discuss the ways in which combined DBS and TMS—for the future personalization of treatment strategies—will further ameliorate post-stroke motor disorders. For example, TMS can be used safely in movement disorder patients with DBS, and pairing DBS with TMS at specific intervals and patterns produces long-term potentiation-like effects related to cortical plasticity. A further characterization of the precise repair mechanisms, together with technological innovations, is likely to substantially improve the efficacy of treatments for post-stroke motor disorders.

The brain–computer interface (BCI) plays an important role in neural restoration. Current BCI systems generally require complex experimental preparation to perform well, but this time-consuming process may hinder their use in clinical applications. To explore the feasibility of simplifying the BCI system setup, a wearable BCI system based on the steady-state visual evoked potential (SSVEP) was developed and evaluated. Fifteen healthy participants were recruited to test the fast-setup system using dry and wet electrodes in a real-life scenario. In this study, the average system setup time for the dry electrode was 38.40 seconds and that for the wet electrode was 103.40 seconds, which are times appreciably shorter than those in previous BCI experiments, enabling a rapid setup of the BCI system. Although the electroencephalogram (EEG) signal quality was low in this fast-setup BCI experiment, the BCI system achieved an information transfer rate of 138.89 bits/min with an eight-channel wet electrode and an information transfer rate of 70.59 bits/min with an eight-channel dry electrode, showing that the overall performance was close to that in traditional experiments. In addition, the results suggest that the solutions of a multi-channel dry electrode or few-channel wet electrode may be suitable for the fast-setup SSEVP-BCI. This fast-setup SSVEP-BCI has the advantages of simple preparation and stable performance and is thus conducive to promoting the use of the BCI in clinical practice.

Background

Stroke is one of the leading causes of death and disability among adults worldwide, and severely impairs the quality of life of patients. Circulating adiponectin (APN) is an endogenous bioactive protein secreted by adipocytes that may have important value in predicting ischemic stroke. In the present study, we aimed to investigate the relationship between circulating APN levels and ischemic stroke.

Methods

The PubMed, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure databases (CNKI) were systematically searched for articles on ‘‘circulating APN’’ and “stroke” published from inception to December 2023. Our analysis included peer-reviewed observational and clinical trial studies reporting odds ratios (OR) and 95% confidence intervals (CI) for ischemic stroke in relation to APN levels. The meta-analysis was performed using a random-effects model to account for between-study heterogeneity. Statistical analyses were performed in STATA 16.

Results

In our analysis, 13 studies and 22,714 individuals were included. There was a significant pooled OR of 1.163 (95% CI: 1.03 to 1.32), suggesting that higher circulating APN levels are associated with an increased risk of ischemic stroke. Furthermore, subgroup analysis indicated region-specific and study design-specific variations in the association between circulating APN levels and ischemic stroke risk. Egger's test revealed no significant publication bias among the included studies (p > 0.05).

Conclusions

Our meta-analysis results suggest that elevated APN levels are associated with an increased risk of ischemic stroke, and support the possible use of APN as a biomarker in stroke prevention strategies. Future research should focus on longitudinal studies and standardized measurement approaches to better understand the potential of APN for predicting and mitigating stroke risk.

Study design

Longitudinal prospective cohort study.

Objectives

To assess the coefficient of efficacy and the influence of various demographic and neurological factors on changes in Spinal Cord Independence Measure III (SCIM-III) scores over time in traumatic spinal cord injury (TSCI) patients.

Setting

Patient recruitment and evaluations were conducted at the Brain and Spinal Injury Research Center in Imam Khomeini Hospital Complex, Tehran, Iran.

Methods

The study was performed over an 8-year period in our outpatient rehabilitation setting. Changes in SCIM-III scores were assessed in 559 TSCI patients (of 1460 enrolled patients) who fit the inclusion criteria. All included patients participated in our outpatient rehabilitation program, which consisted of a multidisciplinary education program combined with occupational therapy, physical therapy, and home nursing as a rehabilitation package for a 6-month period. Patients then received follow-up assessments every 6 months.

Results

Predictors of the SCIM-III score as a rehabilitation outcome tool, and of its change over time, included age (younger patients had better outcomes, p = 0.067), marital status (married patients had better outcomes, p = 0.031), education level (patients with university education had better outcomes, p = 0.003), occupation status (employed patients had better outcomes, p = 0.009), and neurological level of injury (patients with injuries at lower levels had better outcomes, p < 0.001). However, sex and injury severity as per the American Spinal Injury Association Impairment Scale (AIS) had no significant effects on functional outcomes (i.e., SCIM-III score changes over time).

Conclusion

Age, marital status, education level, employment, and neurological level all affected the final SCIM-III scores of SCI patients. By contrast, sex and AIS grade were not significant predictors of SCIM-III outcomes. Further studies that include additional factors may be useful for future SCIM-III models.