Current Neurovascular Research - Online First
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Future Directions in Anxiolytic Therapy: A Comprehensive Review of Novel Targets and Strategies
Authors: Mahima, Avijit Mazumder and Bhavani PentelaAvailable online: 18 August 2025More LessBackgroundWith 301 million cases worldwide, anxiety disorders represent a serious public health concern. Many people endure ongoing distress while receiving several treatments because of the drawbacks of traditional therapy, such as adverse effects, dependence, and inconsistent efficacy. This emphasizes the absolute need for novel treatment approaches.
ObjectiveThis review examines emerging pharmacological and non-pharmacological strategies for anxiety disorders, assessing existing and developing therapeutic options while examining the drawbacks of conventional therapies.
MethodsA comprehensive literature review was carried out using the NIH, PubMed, and Google Scholar databases. Studies from 2020-2025 were given priority in the inclusion criteria, with a few supporting references from earlier years. Personalized medicine, combination therapy, non-pharmacological interventions, and novel anxiolytic targets, etc., were among the keywords used.
ResultsConventional therapies, including benzodiazepines, SSRIs, and SNRIs, are still the major choices, but they have significant disadvantages. The protein kinase pathway, endocannabinoid and orexin systems, NK1R antagonists, and microbiome modulation are examples of emerging targets. Emerging strategies that show preliminary promise include digital therapeutics, gene therapy, optogenetics, personalized medicine, combination therapy, herbal therapy, and peptide-based medicines (e.g., NPY, NPS, oxytocin analogs, CRF, vasopressin, and melanocortin receptor antagonist). Several of these approaches modulate key neural circuits, such as the involvement of the amygdala–prefrontal cortex axis, via the HPA axis, and biomarker-informed personalization, among others; yet many remain in early-phase or preclinical investigation. However, limited comparative data exist between these novel strategies and standard therapies, underlining the need for rigorous head-to-head evaluations.
ConclusionAdvances in molecular neuroscience and precision medicine offer potential alternatives to conventional treatments. However, most emerging therapies require further clinical validation, large-scale trials, and translational refinement before they can be integrated into real-world decision-making for anxiety disorders.
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Exploring the Causal Relationships and Underlying Mechanisms of Genetically Linked Immune Cells with Hemorrhagic Stroke
Authors: Qi Li, Yingjie Shen, Zhao Yu, Yaolou Wang, Yongze Shen, Chunmei Guo, Shang Gao, Hongge Yang, Aili Gao and Hongsheng LiangAvailable online: 11 August 2025More LessIntroductionHemorrhagic stroke is a severe disease that endangers human life and well-being, with unclear pathogenesis. Recent studies have found an association between the immune system and hemorrhagic stroke, but the causal relationship between them remains unclear. We aim to elucidate the causal relationships between immune cell traits and hemorrhagic stroke using Mendelian randomization (MR).
MethodsWe collected genome-wide association studies (GWAS) summary statistics for 731 immune cell traits as exposures, and GWAS data for hemorrhagic stroke outcomes, including intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and cerebral aneurysm (non-ruptured) (CA), from the FinnGen Consortium's R10 dataset. Five methods were employed to evaluate the causal relationships, with the primary method being the inverse-variance weighted (IVW) method. Sensitivity analyses were carried out to enhance the robustness. Subsequently, we performed multivariate MR analyses, including confounding variables. Additionally, reverse MR analyses were carried out. Ultimately, we conducted pathway and functional enrichment analyses.
ResultsAfter univariate and multivariate MR analyses, we identified that the higher counts of herpesvirus entry mediator (HVEM) on effector memory (EM) CD4+ cells (OR=0.954, 95%CI:0.925-0.984, P=0.003, PFDR=0.120) were a protective factor for SAH, and the counts of forward scatter area (FSC-A) on plasmacytoid dendritic cells (DC) (OR=1.059, 95%CI:1.023-1.095, P=0.001, PFDR=0.066) were associated with an increased risk of CA. The reverse MR indicated that CA could significantly increase the effector memory (EM) DN (CD4-CD8-) AC counts. No significant pleiotropy or heterogeneity was calculated in the MR analyses. SNP annotation and enrichment analyses suggested possible mechanisms by which immune cells affect hemorrhagic stroke.
DiscussionThe involvement of immune cells in the neuroinflammatory responses has been demonstrated in previous studies. Among the immune cell traits with a significant causal relationship to hemorrhagic stroke, higher levels of HVEM on EM CD4+ cells may inhibit further inflammatory progress by binding to corresponding receptors, thereby exerting a protective effect against SAH. Alterations in FSC-A values (a flow cytometry measure of cell size) of plasmacytoid dendritic cells may contribute to atherosclerosis through cascading reactions that ultimately lead to CA. In addition, based on existing studies, other immune cell traits and related pathways identified in this study may contribute to the prevention and treatment of hemorrhagic stroke, providing a reference for future research. Finally, this study has some limitations, including population specificity, the use of a relatively lenient significance threshold (P < 1 × 10-5), and potential bias from weak instrumental variables and pleiotropy.
ConclusionThis study demonstrated the causal relationships between immune cell traits and hemorrhagic stroke, laying the foundation for understanding the underlying mechanisms.
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WITHDRAWN: Primary Changes in Corneal Nerve Fiber Structure in Patients with Primary Glaucoma and Related Influencing Factors
Authors: Mingming Cai, Jie Zhang and Lin XieAvailable online: 29 November 2024More LessThe article has been withdrawn at the request of the authors as they could not fulfill the editorial requirements from the editorial office of the journal Current Neurovascular Research.
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