Theta burst stimulation for enhancing upper extremity motor functions after stroke: a systematic review of clinical and mechanistic evidence.

This systematic review aimed to evaluate the effects of different theta burst stimulation (TBS) protocols on improving upper extremity motor functions in patients with stroke, their associated modulators of efficacy, and the underlying neural mechanisms. We conducted a meta-analytic review of 29 controlled trials published from January 1, 2000, to August 29, 2023, which investigated the effects of TBS on upper extremity motor, neurophysiological, and neuroimaging outcomes in poststroke patients. TBS significantly improved upper extremity motor impairment (Hedge's g = 0.646, p = 0.003) and functional activity (Hedge's g = 0.500, p < 0.001) compared to controls. Meta-regression revealed a significant relationship between the percentage of patients with subcortical stroke and the effect sizes of motor impairment (p = 0.015) and functional activity (p = 0.018). Subgroup analysis revealed a significant difference in the improvement of upper extremity motor impairment between studies using 600-pulse and 1200-pulse TBS (p = 0.002). Neurophysiological studies have consistently found that intermittent TBS increases ipsilesional corticomotor excitability. However, evidence to support the regional effects of continuous TBS, as well as the remote and network effects of TBS, is still mixed and relatively insufficient. In conclusion, TBS is effective in enhancing poststroke upper extremity motor function. Patients with preserved cortices may respond better to TBS. Novel TBS protocols with a higher dose may lead to superior efficacy compared with the conventional 600-pulse protocol. The mechanisms of poststroke recovery facilitated by TBS can be primarily attributed to the modulation of corticomotor excitability and is possibly caused by the recruitment of corticomotor networks connected to the ipsilesional motor cortex.

Computational simulation of transcranial magnetic stimulation-induced electric fields in the dorsolateral prefrontal cortex of heavy cannabis using individuals.

We aimed to investigate the influence of demographic and clinical modulators on the strength of transcranial magnetic stimulation (TMS)-induced electric fields (EFs) in the left dorsolateral prefrontal cortex (lDLPFC) in heavy cannabis using individuals. Structural T1-weighted magnetic resonance imaging scans of 20 heavy cannabis using individuals and 22 non-cannabis users (the controls) in the age range of 18-25 were retrieved. Computational simulations of TMS-induced EFs in the lDLPFC were performed. No significant difference in the strength of TMS-induced EFs was observed between heavy cannabis using individuals and the controls. A negative correlation between the scalp-to-cortex distance demonstrated and the strength of the induced EFs. The severity of cannabis use related problems did not correlate with the induced EFs in the lDLPFC of heavy cannabis using individuals. However, the severity of alcohol use related problems was negatively correlated with the induced EF in the lDLPFC localized by the 5-cm method in the whole sample. Early adulthood seems related to an increase in the induced EFs in the lDLPFC. In conclusion, the dominant factor influencing TMS-induced EFs was the scalp-to-cortex distance. In early adulthood, the interaction between age and comorbid substance use may influence with the magnitude of TMS-induced EFs, thereby complicating the treatment effect of TMS in young people with substance use disorders.

Correction: He et al. Impacts of Cigarette Smoke (CS) on Muscle Derangement in Rodents-A Systematic Review. Toxics 2022, 10, 262.

In the original publication [...].

In vitro methods in autophagy research: Applications in neurodegenerative diseases and mood disorders.

Background: Autophagy is a conserved physiological intracellular mechanism responsible for the degradation and recycling of cytoplasmic constituents (e.g., damaged organelles, and protein aggregates) to maintain cell homeostasis. Aberrant autophagy has been observed in neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Huntington's Disease (HD), and recently aberrant autophagy has been associated with mood disorders, such as depression. Several in vitro methods have been developed to study the complex and tightly regulated mechanisms of autophagy. In vitro methods applied to autophagy research are used to identify molecular key players involved in dysfunctional autophagy and to screen autophagy regulators with therapeutic applications in neurological diseases and mood disorders. Therefore, the aims of this narrative review are (1) to compile information on the cell-based methods used in autophagy research, (2) to discuss their application, and (3) to create a catalog of traditional and novel in vitro methods applied in neurodegenerative diseases and depression. Methods: Pubmed and Google Scholar were used to retrieve relevant in vitro studies on autophagy mechanisms in neurological diseases and depression using a combination of search terms per mechanism and disease (e.g., "macroautophagy" and "Alzheimer's disease"). A total of 37 studies were included (14 in PD, 8 in AD, 5 in ALS, 5 in %, and 5 in depression). Results: A repertoire of traditional and novel approaches and techniques was compiled and discussed. The methods used in autophagy research focused on the mechanisms of macroautophagy, microautophagy, and chaperone-mediated autophagy. The in vitro tools presented in this review can be applied to explore pathophysiological mechanisms at a molecular level and to screen for potential therapeutic agents and their mechanism of action, which can be of great importance to understanding disease biology and potential therapeutic options in the context of neurodegenerative disorders and depression. Conclusion: This is the first review to compile, discuss, and provide a catalog of traditional and novel in vitro models applied to neurodegenerative disorders and depression.

Gender-Based Analysis of the Association Between Mental Health, Sleep Quality, Aggression, and Physical Activity Among University Students During the COVID-19 Outbreak.

COVID-19 has spread throughout the world, resulting in significant morbidity, mortality, and negative psychological effects among general population. However, university students are particularly vulnerable in terms of mental health. The present study evaluated the association between mental health, quality of sleep, aggression, and physical activity in university students in Mexico after 1 year of dealing with the COVID-19 pandemic in Mexico, including a gender-sensitive analysis. Participants (935 university students) completed an online questionnaire which collected information regarding demographic data, psychological distress (IES-R scale), depression, anxiety, and stress (DASS-21), aggressiveness Buss-Perry Aggressive Questionnaire, sleep quality (PSQI) and physical activity (IPAQ-S). Findings showed that female students showed significantly higher scores in psychological distress, anxiety, stress scores and sleep quality, as compared to male students. By contrast, male students showed significantly higher scores on aggressiveness than female students. In addition, on physical activity, females performed significantly higher MET-min/week on moderate and high levels. Finally, liner regression model accounted for approximately 73.5% of the variance in DASS-21 scores, with the body mass index, IES-R, Pittsburgh Sleep Quality Index, and IPAQ subscales, emerging as significant individual (positive) predictors. Therefore, the pandemic affected female and male students differently. Female students reported more psychological distress, anxiety, and stress while male students reported higher aggressiveness. The differences observed may be due to physiological differences, the response to stress, and differences in sensitivity to life events.

A Longitudinal Study of the Psychological State of Teachers Before and During the COVID-19 Outbreak in Mexico.

The COVID-19 outbreak significantly impacted people's lives. Within the education system, the teaching mode drastically changed to adapt to the social distancing restrictions due to the pandemic. Consequently, teachers have been facing challenges associated with remote learning in addition to those of the pandemic. The aim of the present study was to assess the psychological state among teachers at two stages: pre-pandemic (November 2019) and during the pandemic (June-July 2020 and June-July 2021). Information regarding demographic data, depression, anxiety, and stress (DASS-21), and burnout syndrome (MBI-ES) was collected using validated questionnaires. Results showed a significantly higher scores as well as a higher prevalence in the DASS-21 and the MBI-ES scales, on the second measurement taken during the pandemic compared to the pre-pandemic period and the first evaluation during the pandemic. During the second evaluation on pandemic stage, female teachers of ≥45 years of age with a college-level of education, 11 years of teaching experience, and currently teaching at preschools and primary schools were significantly associated with higher anxiety, stress, EE, and burnout scores. In addition, female teachers aged ≥45 years reported higher PD and PA scores. Finally, an association between burnout syndrome and depression was identified in the evaluations carried out during the pandemic considering both the total sample and the analysis per gender. The study shows that teachers' mental health has been negatively affected by the pandemic. Efforts from the education system and health authorities are crucial to design and implement strategies to improve teachers' mental health during the fight against COVID-19.

RNA-binding protein signaling in adult neurogenesis.

The process of neurogenesis in the brain, including cell proliferation, differentiation, survival, and maturation, results in the formation of new functional neurons. During embryonic development, neurogenesis is crucial to produce neurons to establish the nervous system, but the process persists in certain brain regions during adulthood. In adult neurogenesis, the production of new neurons in the hippocampus is accomplished via the division of neural stem cells. Neurogenesis is regulated by multiple factors, including gene expression at a temporal scale and post-transcriptional modifications. RNA-binding Proteins (RBPs) are known as proteins that bind to either double- or single-stranded RNA in cells and form ribonucleoprotein complexes. The involvement of RBPs in neurogenesis is crucial for modulating gene expression changes and posttranscriptional processes. Since neurogenesis affects learning and memory, RBPs are closely associated with cognitive functions and emotions. However, the pathways of each RBP in adult neurogenesis remain elusive and not clear. In this review, we specifically summarize the involvement of several RBPs in adult neurogenesis, including CPEB3, FXR2, FMRP, HuR, HuD, Lin28, Msi1, Sam68, Stau1, Smaug2, and SOX2. To understand the role of these RBPs in neurogenesis, including cell proliferation, differentiation, survival, and maturation as well as posttranscriptional gene expression, we discussed the protein family, structure, expression, functional domain, and region of action. Therefore, this narrative review aims to provide a comprehensive overview of the RBPs, their function, and their role in the process of adult neurogenesis as well as to identify possible research directions on RBPs and neurogenesis.

Impacts of Cigarette Smoke (CS) on Muscle Derangement in Rodents-A Systematic Review.

Cigarette smoke (CS) is the major risk factor for chronic obstructive pulmonary disease (COPD) and can induce systemic manifestations, such as skeletal muscle derangement. However, inconsistent findings of muscle derangement were reported in previous studies. The aim of the present study was to consolidate the available evidence and assess the impact of CS on muscle derangement in rodents. A comprehensive literature search of five electronic databases identified ten articles for final analysis. Results showed that the diaphragm, rectus femoris, soleus, and gastrocnemius exhibited significant oxidative to glycolytic fiber conversions upon CS exposure. In contrast, the extensor digitorum longus (EDL), plantaris, and tibialis did not exhibit a similar fiber-type conversion after CS exposure. Hindlimb muscles, including the quadriceps, soleus, gastrocnemius, and EDL, showed significant reductions in the CSA of the muscle fibers in the CS group when compared to the control group. Changes in inflammatory cytokines, exercise capacity, and functional outcomes induced by CS have also been evaluated. CS could induce a shift from oxidative fibers to glycolytic fibers in high-oxidative muscles such as the diaphragm, rectus femoris, and soleus, and cause muscle atrophy, as reflected by a reduction in the CSA of hindlimb muscles such as the quadriceps, soleus, gastrocnemius, and EDL.

Biomarkers for prognostic functional recovery poststroke: A narrative review.

Background and objective: Prediction of poststroke recovery can be expressed by prognostic biomarkers that are related to the pathophysiology of stroke at the cellular and molecular level as well as to the brain structural and functional reserve after stroke at the systems neuroscience level. This study aimed to review potential biomarkers that can predict poststroke functional recovery. Methods: A narrative review was conducted to qualitatively summarize the current evidence on biomarkers used to predict poststroke functional recovery. Results: Neurophysiological measurements and neuroimaging of the brain and a wide diversity of molecules had been used as prognostic biomarkers to predict stroke recovery. Neurophysiological studies using resting-state electroencephalography (EEG) revealed an interhemispheric asymmetry, driven by an increase in low-frequency oscillation and a decrease in high-frequency oscillation in the ipsilesional hemisphere relative to the contralesional side, which was indicative of individual recovery potential. The magnitude of somatosensory evoked potentials and event-related desynchronization elicited by movement in task-related EEG was positively associated with the quantity of recovery. Besides, transcranial magnetic stimulation (TMS) studies revealed the potential values of using motor-evoked potentials (MEP) and TMS-evoked EEG potentials from the ipsilesional motor cortex as prognostic biomarkers. Brain structures measured using magnetic resonance imaging (MRI) have been implicated in stroke outcome prediction. Specifically, the damage to the corticospinal tract (CST) and anatomical motor connections disrupted by stroke lesion predicted motor recovery. In addition, a wide variety of molecular, genetic, and epigenetic biomarkers, including hemostasis, inflammation, tissue remodeling, apoptosis, oxidative stress, infection, metabolism, brain-derived, neuroendocrine, and cardiac biomarkers, etc., were associated with poor functional outcomes after stroke. However, challenges such as mixed evidence and analytical concerns such as specificity and sensitivity have to be addressed before including molecular biomarkers in routine clinical practice. Conclusion: Potential biomarkers with prognostic values for the prediction of functional recovery after stroke have been identified; however, a multimodal approach of biomarkers for prognostic prediction has rarely been studied in the literature. Future studies may incorporate a combination of multiple biomarkers from big data and develop algorithms using data mining methods to predict the recovery potential of patients after stroke in a more precise way.

Effect of a peer-led intervention combining mental health promotion with coping-strategy-based workshops on mental health awareness, help-seeking behavior, and wellbeing among university students in Hong Kong.

BACKGROUND: The psychological well-being of university students is an important factor in successfully coping with the demands of academic life. This study aimed to assess the impact of a peer-led intervention of mental health promotion combined with coping-strategy-based group workshops on mental health awareness and help-seeking behavior among university students in Hong Kong. METHOD: A mixed-method concurrent design was used for this study. Quantitative data, based on one-group pretest-posttest design, were collected using Mental Health Knowledge Schedule Questionnaire to assess mental health awareness, and Attitude Towards Seeking Professional Help Questionnaire-Short Form to examine help-seeking behavior of university students from The Hong Kong Polytechnic University. Qualitative data were collected from written post-activity reflections and focus group discussions which were thematically analyzed. RESULTS: A total of 62 university students (mean age: 23.2 ± 5.1 years) were included in this study. Mental health awareness was significantly improved (p = 0.015, 95% Confidence Interval of - 2.670, - 0.297) after program implementation. Help-seeking behavior mean score increased from pretest to posttest, however, no significant difference was observed (p = 0.188, 95% CI = - 1.775, 0.355). Qualitative analysis revealed that the program helped participants learn about coping strategies to help themselves and others with mental health challenges. CONCLUSIONS: The peer-led intervention provided a positive impact through increased mental health awareness and knowledge of coping strategies on self-help and helping others among university students. Further study could focus on the impact of the program when applied regularly throughout the entire academic year.

Molecular Targets of Bis (7)-Cognitin and Its Relevance in Neurological Disorders: A Systematic Review.

Background: The exact mechanisms involved in the pathogenesis of neurodegenerative conditions are not fully known. The design of drugs that act on multiple targets represents a promising approach that should be explored for more effective clinical options for neurodegenerative disorders. B7C is s synthetic drug that has been studied for over 20 years and represents a promising multi-target drug for the treatment of neurodegenerative disorders, such as AD. Aims: The present systematic review, thus, aims at examining existing studies on the effect of B7C on different molecular targets and at discussing the relevance of B7C in neurological disorders. Methods: A list of predefined search terms was used to retrieve relevant articles from the databases of Embase, Pubmed, Scopus, and Web of Science. The selection of articles was done by two independent authors, who were considering articles concerned primarily with the evaluation of the effect of B7C on neurological disorders. Only full-text articles written in English were included; whereas, systematic reviews, meta-analyses, book chapters, conference subtracts, and computational studies were excluded. Results: A total of 2,266 articles were retrieved out of which 41 articles were included in the present systematic review. The effect of B7C on molecular targets, including AChE, BChE, BACE-1, NMDA receptor, GABA receptor, NOS, and Kv4.2 potassium channels was evaluated. Moreover, the studies that were included assessed the effect of B7C on biological processes, such as apoptosis, neuritogenesis, and amyloid beta aggregation. The animal studies examined in the review focused on the effect of B7C on cognition and memory. Conclusions: The beneficial effects observed on different molecular targets and biological processes relevant to neurological conditions confirm that B7C is a promising multi-target drug with the potential to treat neurological disorders.

Lavender essential oil ameliorates depression-like behavior and increases neurogenesis and dendritic complexity in rats.

Depression is a major health issue that causes severe societal economic and health burden. Aromatherapy, a practice that uses essential oils for preventive and therapeutic purposes, represents a promising therapeutic alternative for the alleviation of depressive symptoms. Lavender essential oil (LEO) has been the focus of clinical studies due to its positive effect on mood. An animal model of chronic administration of high dose corticosterone to induce depression- and anxiety-like behavior and reduced neurogenesis was used to explore the biological changes brought by aromatherapy. Twenty-four adult male Sprague Dawley rats were randomly assigned into four groups: Control, corticosterone (Cort) group with high dose of corticosterone, LEO group with daily exposure to LEO by inhalation, and LEO + Cort. At the end of the 14-day treatment period, behavioral tests were carried out. Serum samples were collected 2-3 days after the 14-day period treatment and before perfusion to carry out biochemical analyses to measure BDNF, corticosterone and oxytocin. After perfusion, brains were collected for immunohistochemical analysis to detect BrdU and DCX positive cells in the hippocampus and subventricular zone. Results showed that treatment with LEO ameliorated the depression-like behavior induced by the chronic administration of corticosterone as observed in the LEO + Cort group. Cort treatment reduced the number of BrdU positive cells in the hippocampus and the subventricular zone. Treatment with LEO prevented the corticosterone-induced reduction in the number of BrdU positive cells (LEO + Cort group) demonstrating the neurogenic effect of LEO under high corticosterone conditions. Chronic administration of high dose of corticosterone significantly reduced the dendritic complexity of immature neurons. On the contrary, treatment with LEO increased dendritic complexity of immature neurons under high corticosterone conditions (LEO + Cort group). The improved neurogenesis and dendritic complexity observed in the LEO + Cort group demonstrated a clear restorative effect of LEO under high corticosterone conditions. However, 2-3 days after the treatment, the levels of BDNF were upregulated in the LEO and LEO + Cort groups. Furthermore, the concentration of oxytocin in serum, 2-3 days after the treatment, showed to be upregulated in the LEO group alone. The present study has provided evidence of the biological effect of LEO on neuroplasticity and neurogenesis. Also, this study contributes to the understanding of the mechanism of action of LEO in an animal model where depression- and anxiety-like behavior and reduced neurogenesis were induced by high corticosterone administration.

Exogenous neural stem cell transplantation for cerebral ischemia.

Cerebral ischemic injury is the main manifestation of stroke, and its incidence in stroke patients is 70-80%. Although ischemic stroke can be treated with tissue-type plasminogen activator, its time window of effectiveness is narrow. Therefore, the incidence of paralysis, hypoesthesia, aphasia, dysphagia, and cognitive impairment caused by cerebral ischemia is high. Nerve tissue regeneration can promote the recovery of the aforementioned dysfunction. Neural stem cells can participate in the reconstruction of the damaged nervous system and promote the recovery of nervous function during self-repair of damaged brain tissue. Neural stem cell transplantation for ischemic stroke has been a hot topic for more than 10 years. This review discusses the treatment of ischemic stroke with neural stem cells, as well as the mechanisms of their involvement in stroke treatment.

Protective effect of Lycium Barbarum polysaccharides on dextromethorphan-induced mood impairment and neurogenesis suppression.

Dextromethorphan (DXM) is one of the common drugs abused by adolescents. It is the active ingredient found in cough medicine which is used for suppressing cough. High dosage of DXM can induce euphoria, dissociative effects and even hallucinations. Chronic use of DXM may also lead to depressive-related symptoms. Lycium barbarum, commonly known as wolfberry, has been used as a traditional Chinese medicine for the treatment of ageing-related neurodegenerative diseases. A recent study has shown the potential beneficial effect of Lycium barbarum to reduce depression-like behavior. In the present study, we investigated the role of Lycium barbarum polysaccharide (LBP) to alleviate DXM-induced emotional distress. Sprague Dawley rats were divided into 4 groups (n=6 per group), including the normal control (vehicles only), DXM-treated group (40 mg/kg DXM), LBP-treated group (1 mg/kg LBP) and DXM+ LBP-treated group (40 mg/kg DXM and 1 mg/kg LBP). After two-week treatment, the DXM-treated group showed increased depression-like and social anxiety-like behaviors in the forced swim test and social interaction test respectively. On the other hand, the adverse behavioral effects induced by DXM were reduced by LBP treatment. Histological results showed that LBP treatment alone did not promote hippocampal neurogenesis when compared to the normal control, but LBP could lessen the suppression of hippocampal neurogenesis induced by DXM. The findings provide insights for the potential use of wolfberry as an adjunct treatment option for alleviating mood disturbances during rehabilitation of cough syrup abusers.

The Use of Omic Technologies Applied to Traditional Chinese Medicine Research.

Natural products represent one of the most important reservoirs of structural and chemical diversity for the generation of leads in the drug development process. A growing number of researchers have shown interest in the development of drugs based on Chinese herbs. In this review, the use and potential of omic technologies as powerful tools in the modernization of traditional Chinese medicine are discussed. The analytical combination from each omic approach is crucial for understanding the working mechanisms of cells, tissues, organs, and organisms as well as the mechanisms of disease. Gradually, omic approaches have been introduced in every stage of the drug development process to generate high-quality Chinese medicine-based drugs. Finally, the future picture of the use of omic technologies is a promising tool and arena for further improvement in the modernization of traditional Chinese medicine.

The Effectiveness of Aromatherapy for Depressive Symptoms: A Systematic Review.

Background. Depression is one of the greatest health concerns affecting 350 million people globally. Aromatherapy is a popular CAM intervention chosen by people with depression. Due to the growing popularity of aromatherapy for alleviating depressive symptoms, in-depth evaluation of the evidence-based clinical efficacy of aromatherapy is urgently needed. Purpose. This systematic review aims to provide an analysis of the clinical evidence on the efficacy of aromatherapy for depressive symptoms on any type of patients. Methods. A systematic database search was carried out using predefined search terms in 5 databases: AMED, CINHAL, CCRCT, MEDLINE, and PsycINFO. Outcome measures included scales measuring depressive symptoms levels. Results. Twelve randomized controlled trials were included and two administration methods for the aromatherapy intervention including inhaled aromatherapy (5 studies) and massage aromatherapy (7 studies) were identified. Seven studies showed improvement in depressive symptoms. Limitations. The quality of half of the studies included is low, and the administration protocols among the studies varied considerably. Different assessment tools were also employed among the studies. Conclusions. Aromatherapy showed potential to be used as an effective therapeutic option for the relief of depressive symptoms in a wide variety of subjects. Particularly, aromatherapy massage showed to have more beneficial effects than inhalation aromatherapy.

Repeated treatment with oxytocin promotes hippocampal cell proliferation, dendritic maturation and affects socio-emotional behavior.

Rewarding social behaviors including positive social interactions and sexual behaviors are shown to regulate adult neurogenesis, but the underlying biological mechanisms remain elusive. Oxytocin, a neurohypophysial hormone secreted after exposure to social interaction or sexual behaviors, has a profound role in the formation of social bonding and regulation of emotional distress. While the acute effect of oxytocin was usually studied, relatively scarce evidence showed the behavioral consequence of repeated oxytocin treatment. The purpose of the current study was to investigate the effect of repeated oxytocin treatment on hippocampal cell proliferation, dendritic maturation of new born neurons and social/emotional behaviors. Adult male Sprague-Dawley rats received treatment with either vehicle or oxytocin (1mg/kg) daily for two weeks. Behavioral tests revealed that oxytocin increased social behaviors and reduced the anxiety- and depression-like behaviors. Cell proliferation, differentiation and the dendritic complexity of new born neurons in the hippocampus were promoted by oxytocin treatment. Depression- and anxiety-like behaviors were induced by repeated treatment of corticosterone (40mg/kg) for two weeks while oxytocin treatment reversed the behavioral disturbances. Suppression of cell proliferation caused by corticosterone was reverted by oxytocin treatment in which cell proliferation, cell differentiation, and dendritic complexity increased. The present findings reveal that oxytocin not only enhances cell proliferation, but also promotes the development of the new neurons which is associated with the induction of positive emotional and social behaviors. The results also suggest that oxytocin may be a potential therapeutic agent for treatment of emotional and social dysfunction.