Weimin Zhang

Narcolepsy type 1 (NT1) is a chronic neurological disorder characterized mainly by impaired wakefulness maintenance and dysregulated rapid eye movement (REM) sleep, which markedly affects patients’ daytime functioning and quality of life. The core pathological basis of NT1 is the selective loss of orexinergic neurons. The orexinergic system regulates histaminergic neurons in the tuberomammillary nucleus (TMN) through anatomical projections and functional excitation, while the histaminergic system contributes to cortical activation, arousal maintenance, and attention regulation. Therefore, the orexinergic and histaminergic systems can be regarded as interconnected and functionally complementary components of the arousal network. Previous studies have suggested alterations in histaminergic signaling in NT1, although the specific mechanisms underlying its role in NT1 remain incompletely understood. Current evidence suggests that histamine may play a modulatory role in NT1-associated phenotypes. This review summarizes the physiological functions of the histaminergic system in arousal regulation and discusses its interaction with the orexinergic system. It further analyzes the role of HA in NT1, its influence on clinical phenotypes, and related therapeutic strategies, with the aim of providing insights for mechanistic research and precision treatment of NT1.

Alzheimer’s disease treatment is shifting from pathology removal to regulating the brain microenvironment. Anti-Aβ monoclonal antibodies, such as lecanemab and donanemab, provide statistically significant disease-modifying effects but offer only modest cognitive improvement and pose safety risks, including amyloid-related imaging abnormalities. These results show that amyloid clearance is clinically relevant but not sufficient for full restoration of neuroimmune, metabolic, synaptic, and neurovascular balance. Microglia are now seen as central to Alzheimer’s disease susceptibility and progression, existing along dynamic, spatially organized, sex-influenced, and genetically determined continua beyond a simple pro- or anti-inflammatory state. This review calls out three key drivers of microglial dysfunction: the TREM2–APOE lipid-sensing axis, complement-mediated synaptic elimination, and immunometabolic reprogramming—including glycolysis, mitochondrial damage, autophagy failure, NAD+ depletion, and innate immune signaling. We examine natural bioactive compounds, metabolic modulators, and biomimetic nanodelivery as promising, yet currently unproven, strategies for adjusting microglial state. Future therapies should incorporate both pathology removal and microenvironment protection, tailored by disease stage, genetic profile, sex, vascular risk, and microglial state-associated biomarkers.

Introduction: Sleep disorders represent the most prevalent psychiatric complication following stroke, seriously impacting patients' neurological recovery, functional prognosis, and quality of life. Music therapy, as a safe, cost-effective, and non-invasive intervention, is widely employed to ameliorate post-stroke sleep disorders. However, the precise mechanisms underlying music therapy's effects on post-stroke sleep disorders require further elucidation. This review aims to systematically examine the efficacy of music therapy for post-stroke sleep disorders and to elucidate the underlying physiological mechanisms through which music may improve sleep outcomes in this population. Methods: We conducted a systematic search across the Cochrane Library, PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP, with a search time frame ending in August 2025. Quality assessment was performed using the Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). Results: A total of 1,363 subjects from 14 original articles met the criteria for inclusion in the systematic review. Each study has shown that music intervention can effectively improve the sleep status in patients with post-stroke sleep disorders.

Ischemic stroke (IS) is a severe central nervous system disorder characterized by high incidence, disability, mortality, and recurrence rates, along with numerous complications. The microbiota-gut-brain axis (MGBA) represents a bidirectional communication pathway between the brain and the gut, which can influence the onset and progression of IS through neural, immunoregulatory, and gut metabolite pathways. Recent preclinical and clinical evidence supports the use of fecal microbiota transplantation (FMT), probiotics and prebiotics, dietary interventions, and antibiotics as strategies to suppress neuroinflammation in IS, protect the blood-brain barrier, modulate immune responses, and improve stroke outcomes. In this review, we summarize the manifestations of innate inflammation and adaptive immunity following the onset of IS, highlight the interactions between the MGBA and post-stroke neuroinflammation, and discuss current therapeutic measures, thus providing insights for the development of novel treatment strategies in the future.

Background: The causal relationship between cathepsins and neurological diseases remains uncertain. To address this, we utilized a two-sample Mendelian randomization (MR) approach to assess the potential causal effect of cathepsins on the development of neurological diseases.Methods: This study conducted a two-sample two-way MR study using pooled data from published genome-wide association studies to evaluate the relationship between 10 cathepsins (B, D, E, F, G, H, L2, O, S, and Z) and 7 neurological diseases, which included ischemic stroke, cerebral hemorrhage, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, and epilepsy. The analysis employed various methods such as inverse variance weighting (IVW), weighted median, MR Egger regression, MR pleiotropy residual sum and outlier, Cochran Q statistic, and leave-one-out analysis.Results: We found a causal relationship between cathepsins and neurological diseases, including Cathepsin B and Parkinson’s disease (IVW odds ratio (OR): 0.89, 95% confidence interval (CI): 0.83, 0.95, p = 0.001); Cathepsin D and Parkinson’s disease (OR: 0.80, 95%CI: 0.68, 0.95, p = 0.012); Cathepsin E and ischemic stroke (OR: 1.05, 95%CI: 1.01, 1.09, p = 0.015); Cathepsin O and ischemic stroke (OR: 1.05, 95%CI: 1.01, 1.10, p = 0.021). Reverse MR analyses revealed that multiple sclerosis and Cathepsin E (OR: 1.05, 95%CI: 1.01, 1.10, p = 0.030). There is currently no significant relationship has been found between other cathepsins and neurological diseases.Conclusion: Our study reveals a causal relationship between Cathepsins B, D, E, and O and neurological diseases, offering valuable insights for research aimed at improving the diagnosis and treatment of such conditions.

Objective: There is conflicting published research about the clinical effectiveness of repetitive transcranial magnetic stimulation (rTMS) for the treatment of post-stroke depression (PSD). In order to provide trustworthy information for upcoming therapeutic treatments, this review attempts to compile and assess the data from pertinent systematic reviews and meta-analyses.Methods: The systematic evaluation of repetitive transcranial magnetic stimulation for post-stroke depression was collected by searching CNKI, VIP, Wanfang Database, CBM, PubMed, EMBASE, Web of Science, and Cochrane Library. The retrieval time is from database construction to September 2022. After selection, the included literature was evaluated for methodological quality, reporting quality, and evidence quality using AMSTAR2, PRISMA statements, and the GRADE system.Results: There were a total of 13 studies included, with three having generally comprehensive reporting according to the PRISMA statement, eight having some reporting issues, two having pretty substantial information issues, and 13 having extremely poor methodological quality according to the AMSTAR2. The GRADE was used to grade the quality of the evidence, and the included literature had 0 high-level evidence, eight medium-level evidence, 12 low-level evidence, and 22 very low-level evidence.Limitations: The results of this study are from researchers' subjective evaluation and only qualitative analysis, not quantitative evaluation. Although repeated cross-evaluation of researchers is carried out, the results will be personal. The interventions included in the study were complex, and it was impossible to analyze their effect values quantitatively.Conclusion: Patients with post-stroke depression may benefit from repetitive transcranial magnetic stimulation. However, in terms of the quality of the reports, the methodology, and the quality of the evidence, published systematic evaluations/meta-analyses are of low quality. We list the drawbacks of the current clinical trials of repetitive transcranial magnetic stimulation for post-stroke depression as well as potential therapeutic mechanisms. This information may serve as a guide for future clinical trials aiming to establish a solid foundation for the clinical efficacy of repetitive transcranial magnetic stimulation in the treatment of post-stroke depression.