Abnormally high shear stress (HSS) is strongly associated with intracranial aneurysm (IA) formation. Endothelial Piezo1 is sensitive to shear stress stimulation, but the mechanism by which it mediates this mechanobiological coupling process is unclear.
Methods
The correlation between shear stress and the Piezo1 expression was investigated using human IA samples and a parallel-plate flow chamber system. To determine the effects of endothelial Piezo1 on the phenotype of neighboring vascular smooth muscle cells (VSMCs) and IA formation, the CRISPR/Cas9 system was used to inhibit endothelial Piezo1 gene expression in vitro. Piezo1ΔEC mice were produced by injecting AAV2-BR1-Tie2-Cre into 8-week-old male Piezo1flox/flox mice, which were further used to construct the IA mouse model. Single-cell RNA sequencing and intercellular communication analyses of co-cultured endothelial cells (ECs) and VSMCs were used to screen for receptor-ligand pairs after inhibiting EC Piezo1 in vitro. The role of the screened receptor-ligand pair was further validated via in vivo and in vitro experiments. Additionally, the underlying mechanisms were investigated.
Result
Piezo1 expression correlated negatively with the shear stress in human IA. HSS reduced EC Piezo1 expression and promoted VSMC phenotypic transformation compared with physiological shear stress. Depletion of EC Piezo1 resulted in the VSMC phenotypic transformation and, more importantly, promoted aneurysmal vascular remodeling in the mouse IA model. The platelet-derived growth factor subunit B (PDGFB)_Platelet-derived growth factor receptor β (PDGFRβ) was identified as being involved in this process. Moreover, the PDGFRβ antagonist reversed the VSMC phenotypic transformation and attenuated IA progression. Mechanistically, Piezo1 depletion promoted PDGFB expression via YAP/β-catenin pathway.
Conclusion
HSS downregulates Piezo1 expression in ECs, which subsequently enhances PDGF-BB expression through the YAP/β-catenin signaling pathway. The elevated PDGF-BB facilitates phenotypic transition of VSMCs via PDGFRβ binding, ultimately contributing to IA formation.
{"title":"High Shear Stress-Induced Endothelial Piezo1 Downregulation Promotes Intracranial Aneurysm Formation via the PDGF-BB/PDGFRβ Paracrine Signaling Pathway","authors":"Zhiwen Lu, Sisi Li, Fengfeng Xu, Haishuang Tang, Shijie Zhu, Chuanchuan Wang, Xiaohua Yang, Qinghai Huang","doi":"10.1002/cns.70715","DOIUrl":"10.1002/cns.70715","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Abnormally high shear stress (HSS) is strongly associated with intracranial aneurysm (IA) formation. Endothelial Piezo1 is sensitive to shear stress stimulation, but the mechanism by which it mediates this mechanobiological coupling process is unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The correlation between shear stress and the Piezo1 expression was investigated using human IA samples and a parallel-plate flow chamber system. To determine the effects of endothelial Piezo1 on the phenotype of neighboring vascular smooth muscle cells (VSMCs) and IA formation, the CRISPR/Cas9 system was used to inhibit endothelial Piezo1 gene expression in vitro. Piezo1<sup>ΔEC</sup> mice were produced by injecting AAV2-BR1-Tie2-Cre into 8-week-old male Piezo1<sup>flox/flox</sup> mice, which were further used to construct the IA mouse model. Single-cell RNA sequencing and intercellular communication analyses of co-cultured endothelial cells (ECs) and VSMCs were used to screen for receptor-ligand pairs after inhibiting EC Piezo1 in vitro. The role of the screened receptor-ligand pair was further validated via in vivo and in vitro experiments. Additionally, the underlying mechanisms were investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>Piezo1 expression correlated negatively with the shear stress in human IA. HSS reduced EC Piezo1 expression and promoted VSMC phenotypic transformation compared with physiological shear stress. Depletion of EC Piezo1 resulted in the VSMC phenotypic transformation and, more importantly, promoted aneurysmal vascular remodeling in the mouse IA model. The platelet-derived growth factor subunit B (PDGFB)_Platelet-derived growth factor receptor β (PDGFRβ) was identified as being involved in this process. Moreover, the PDGFRβ antagonist reversed the VSMC phenotypic transformation and attenuated IA progression. Mechanistically, Piezo1 depletion promoted PDGFB expression via YAP/β-catenin pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>HSS downregulates Piezo1 expression in ECs, which subsequently enhances PDGF-BB expression through the YAP/β-catenin signaling pathway. The elevated PDGF-BB facilitates phenotypic transition of VSMCs via PDGFRβ binding, ultimately contributing to IA formation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12745340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tao Yin, Zilei Tian, Lei Lan, Zhengjie Li, Mailan Liu, Yujie Gao, Fanrong Liang, Fang Zeng
Aims
To identify the functional brain connectivity patterns that were correlated with headache and mental conditions in migraineurs and then to elucidate their neurotransmitter basis and explore the potential clinical implications.
Methods
Eighty patients with migraine without aura (MwoA) and 94 healthy controls (HCs) were included. Firstly, we employed partial least–squares correlation (PLSC) to identify a set of resting–state functional connectivity (RSFC) that was co–related with headache symptoms and mental conditions in MwoA patients. Then, we investigated the specific neurotransmitter basis underlying headache–mental disorders-related RSFC patterns. Finally, we explored the potentials of these RSFC patterns in discriminating patients from HCs, interpreting patient symptoms, stratifying patients into subgroups, and predicting treatment outcomes.
Results
The PLSC analysis revealed one robust latent component linking RSFC between the subcortical nuclei (in particular the thalamus and basal ganglia) and the occipital/temporal cortex to the headache–mental conditions in MwoA patients. These RSFC patterns were spatially correlated with the distribution of several neurotransmitters including 5HT1a, 5HT2a, and mGluR5 receptors. The third part of the analysis indicated that the RSFC patterns could discriminate MwoA patients from HCs with an accuracy of 0.793, differentiate patients into two subtypes, and to some extent predict the efficacy of acupuncture treatment.
Conclusion
This was the first “doubly” multivariate analysis identifying functional brain connectivity patterns underlying headache–mental disorder comorbidity in migraineurs. These findings reveal a neurobiological substrate for migraine–mental disorder comorbidity and highlight the potential of these connectivity patterns as biomarkers for diagnosis and treatment prediction.
{"title":"Functional Brain Connectivity Patterns of Headache–Mental Disorder Comorbidity in Patients With Migraine","authors":"Tao Yin, Zilei Tian, Lei Lan, Zhengjie Li, Mailan Liu, Yujie Gao, Fanrong Liang, Fang Zeng","doi":"10.1002/cns.70710","DOIUrl":"10.1002/cns.70710","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To identify the functional brain connectivity patterns that were correlated with headache and mental conditions in migraineurs and then to elucidate their neurotransmitter basis and explore the potential clinical implications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eighty patients with migraine without aura (MwoA) and 94 healthy controls (HCs) were included. Firstly, we employed partial least–squares correlation (PLSC) to identify a set of resting–state functional connectivity (RSFC) that was co–related with headache symptoms and mental conditions in MwoA patients. Then, we investigated the specific neurotransmitter basis underlying headache–mental disorders-related RSFC patterns. Finally, we explored the potentials of these RSFC patterns in discriminating patients from HCs, interpreting patient symptoms, stratifying patients into subgroups, and predicting treatment outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The PLSC analysis revealed one robust latent component linking RSFC between the subcortical nuclei (in particular the thalamus and basal ganglia) and the occipital/temporal cortex to the headache–mental conditions in MwoA patients. These RSFC patterns were spatially correlated with the distribution of several neurotransmitters including 5HT1a, 5HT2a, and mGluR5 receptors. The third part of the analysis indicated that the RSFC patterns could discriminate MwoA patients from HCs with an accuracy of 0.793, differentiate patients into two subtypes, and to some extent predict the efficacy of acupuncture treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This was the first “doubly” multivariate analysis identifying functional brain connectivity patterns underlying headache–mental disorder comorbidity in migraineurs. These findings reveal a neurobiological substrate for migraine–mental disorder comorbidity and highlight the potential of these connectivity patterns as biomarkers for diagnosis and treatment prediction.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12741590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145831725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bao-Lei Xu, Xiu-Lin Liu, Olivier Barret, Gilles D. Tamagnan, Hong-Wen Qiao, Jie Lu, Chun Zhang, Piu Chan, Shu-Ying Liu
Background
The pathophysiology and neural substrates of depression in Parkinson's disease remain unclear. It has been associated with dysregulation of the monoaminergic systems. Furthermore, functional abnormalities within the mesolimbic-basal ganglia reward circuit may be involved in the pathogenesis of Parkinson's disease-related depression.
Objectives
We aimed to investigate monoaminergic deficits and the corresponding changes within the striatum-mesolimbic circuitry in patients with Parkinson's disease and depression.
Methods
This study included eight depressed and 18 non-depressed patients with Parkinson's disease and 28 matched healthy controls. We simultaneously obtained 18F-fluoropropyl-dihydrotetrabenazine positron emission tomography (18F-FP-DTBZ PET) and resting-state functional magnetic resonance images (rs-fMRI). We also recruited additional patients with Parkinson's disease (nine depressed and 20 non-depressed) for the validation of the rs-fMRI analysis. The 18F-FP-DTBZ standardized uptake value ratio relative to the occipital lobe was used to quantify monoaminergic deficits in the striatum-mesolimbic subregion. Voxel- and volume-of-interest-based analyses were performed to investigate the functional connectivity changes in the striatum-mesolimbic circuitry of depressed patients.
Results
Patients who were depressed exhibited greater monoaminergic deficits in the anterior dorsal and ventral putamen and the nucleus-accumbens than non-depressed patients did. Depression severity was negatively correlated with standardized uptake value ratio in the anterior ventral putamen and the nucleus-accumbens of patients with Parkinson's disease. Compared with non-depressed patients, higher functional connectivity was noted within the striatum-mesolimbic circuit in depressed patients.
Conclusions
In depressed Parkinson's disease patients, monoaminergic deficits are present alongside abnormally increased connectivity within the striatum-mesolimbic circuitry, highlighting this pathway as a potential target for treatment.
{"title":"Monoamine Loss and Functional Connectivity Alterations in Patients With Parkinson's Disease and Depression","authors":"Bao-Lei Xu, Xiu-Lin Liu, Olivier Barret, Gilles D. Tamagnan, Hong-Wen Qiao, Jie Lu, Chun Zhang, Piu Chan, Shu-Ying Liu","doi":"10.1002/cns.70705","DOIUrl":"10.1002/cns.70705","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The pathophysiology and neural substrates of depression in Parkinson's disease remain unclear. It has been associated with dysregulation of the monoaminergic systems. Furthermore, functional abnormalities within the mesolimbic-basal ganglia reward circuit may be involved in the pathogenesis of Parkinson's disease-related depression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>We aimed to investigate monoaminergic deficits and the corresponding changes within the striatum-mesolimbic circuitry in patients with Parkinson's disease and depression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included eight depressed and 18 non-depressed patients with Parkinson's disease and 28 matched healthy controls. We simultaneously obtained <sup>18</sup>F-fluoropropyl-dihydrotetrabenazine positron emission tomography (<sup>18</sup>F-FP-DTBZ PET) and resting-state functional magnetic resonance images (rs-fMRI). We also recruited additional patients with Parkinson's disease (nine depressed and 20 non-depressed) for the validation of the rs-fMRI analysis. The <sup>18</sup>F-FP-DTBZ standardized uptake value ratio relative to the occipital lobe was used to quantify monoaminergic deficits in the striatum-mesolimbic subregion. Voxel- and volume-of-interest-based analyses were performed to investigate the functional connectivity changes in the striatum-mesolimbic circuitry of depressed patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients who were depressed exhibited greater monoaminergic deficits in the anterior dorsal and ventral putamen and the nucleus-accumbens than non-depressed patients did. Depression severity was negatively correlated with standardized uptake value ratio in the anterior ventral putamen and the nucleus-accumbens of patients with Parkinson's disease. Compared with non-depressed patients, higher functional connectivity was noted within the striatum-mesolimbic circuit in depressed patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In depressed Parkinson's disease patients, monoaminergic deficits are present alongside abnormally increased connectivity within the striatum-mesolimbic circuitry, highlighting this pathway as a potential target for treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12741543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145831758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu Wang, Beining Yang, Ling Wang, Haotian Xin, Qunya Qi, Yulong Jia, Xianglin Guo, Weimin Zheng, Xin Chen, Fang Li, Qian Chen, Jubao Du, Jie Lu, Nan Chen
Aims
To investigate the alterations in effective brain connectivity in pediatric patients with spinal cord injury (SCI), to reveal the mechanism of brain network reorganization and to identify potential key targets for therapeutic neuromodulation interventions.
Methods
This study enrolled 37 pediatric patients with SCI (24 with complete SCI, 13 with incomplete SCI) and 37 matched healthy controls. All participants underwent resting-state functional MRI. Independent component analysis was conducted to identify intrinsic brain networks and obtain key regions of interest. Dynamic causal modeling (DCM) was applied to further analyze the effective connectivity (EC).
Results
Patients with SCI showed significantly reduced connectivity between the default mode network (DMN) and the salience network (SAN). DCM revealed that the posterior cingulate cortex (PCC) was a key upstream regulator, exerting enhanced inhibitory influence on the medial prefrontal cortex, bilateral insula, and bilateral inferior parietal lobule. Subgroup analyses revealed that complete SCI was associated with increased excitatory drive from the DMN to the SAN, but enhanced inhibitory influence in the reverse pathway compared to incomplete SCI.
Conclusion
The PCC is a pivotal node in post-SCI brain reorganization, suggesting it as a potential neuromodulation target. The bidirectional DMN-SAN regulatory imbalance is closely related to SCI severity.
{"title":"Effective Connectivity Alterations of Directed Brain Network in Pediatric Patients With Spinal Cord Injury","authors":"Yu Wang, Beining Yang, Ling Wang, Haotian Xin, Qunya Qi, Yulong Jia, Xianglin Guo, Weimin Zheng, Xin Chen, Fang Li, Qian Chen, Jubao Du, Jie Lu, Nan Chen","doi":"10.1002/cns.70720","DOIUrl":"10.1002/cns.70720","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To investigate the alterations in effective brain connectivity in pediatric patients with spinal cord injury (SCI), to reveal the mechanism of brain network reorganization and to identify potential key targets for therapeutic neuromodulation interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study enrolled 37 pediatric patients with SCI (24 with complete SCI, 13 with incomplete SCI) and 37 matched healthy controls. All participants underwent resting-state functional MRI. Independent component analysis was conducted to identify intrinsic brain networks and obtain key regions of interest. Dynamic causal modeling (DCM) was applied to further analyze the effective connectivity (EC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with SCI showed significantly reduced connectivity between the default mode network (DMN) and the salience network (SAN). DCM revealed that the posterior cingulate cortex (PCC) was a key upstream regulator, exerting enhanced inhibitory influence on the medial prefrontal cortex, bilateral insula, and bilateral inferior parietal lobule. Subgroup analyses revealed that complete SCI was associated with increased excitatory drive from the DMN to the SAN, but enhanced inhibitory influence in the reverse pathway compared to incomplete SCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The PCC is a pivotal node in post-SCI brain reorganization, suggesting it as a potential neuromodulation target. The bidirectional DMN-SAN regulatory imbalance is closely related to SCI severity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12741492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145831773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>We have carefully reviewed the article titled “Network Pharmacology-Based and Experimental Validation Elucidate the Target Mechanism of Vinorine in Ameliorating Secondary Brain Injury After Intracerebral Hemorrhage” by Wu et al. [<span>1</span>].</p><p>Through a combination of network pharmacology and in vitro/in vivo experiments, the authors propose that Vinorine (Vin) mitigates secondary damage following intracerebral hemorrhage by modulating the CXCR2–JAK–STAT pathway, downregulating MMP expression, and promoting neuronal survival. This study provides important clues regarding the potential of natural products in treating cerebral hemorrhage. We would like to offer some suggestions to further enhance the reliability and completeness of the research.</p><p>Firstly, intraperitoneal (ip) administration was employed in this study. While this route facilitates animal experimentation, the drug must first enter the central nervous system via the peripheral circulation. Peripheral metabolism and immune regulation may influence the assessment of direct central effects. In contrast, intrathecal, intracerebroventricular, or intrastriatal injection allows for more direct targeting of the lesion site [<span>2, 3</span>], thereby better facilitating the validation of Vin's central target effects; or intravenous injection, which is commonly used in clinical practice, also has certain advantages in terms of drug distribution and metabolism, and can provide a reference that is closer to clinical reality for the study. However, regardless of the new injection method used, appropriate toxicological validation should be conducted to ensure its safety and efficacy. Secondly, the authors observed that Vin can restore the integrity of the blood–brain barrier. CXCR2 is primarily expressed on neutrophils [<span>4</span>], which are known to disrupt the integrity of the blood–brain barrier through infiltration [<span>5</span>]. Although studies have shown that CXCR2 expression also increases during the activation of microglia [<span>6</span>], the authors did not perform immunofluorescence colocalization of CXCR2 with either microglia or neutrophils. Therefore, the reduction of CXCR2 expression by Vin may be achieved through the decrease of neutrophil infiltration. We propose that this effect may offer an alternative mechanism: BBB repair reduces the infiltration of peripheral immune cells—such as neutrophils—into brain parenchyma, thereby alleviating local inflammation [<span>7</span>]. This suggests that Vin's neuroprotective effects may not solely depend on regulating the JAK–STAT pathway in microglia, but also involve inhibiting the invasion of peripheral immune cells.</p><p>Therefore, subsequent studies may consider combining single-cell transcriptome sequencing with flow cytometry. By comparing the Vin-treated group with the vehicle control group, it could be interesting to analyze whether the ratio of neutrophils changes and to explore the potential effects o
{"title":"Comments on “Network Pharmacology-Based and Experimental Validation Elucidate the Target Mechanism of Vinorine in Ameliorating Secondary Brain Injury After Intracerebral Hemorrhage”","authors":"Xihan Ying, Jieqi Zhang, Ruijie Ma","doi":"10.1002/cns.70722","DOIUrl":"10.1002/cns.70722","url":null,"abstract":"<p>We have carefully reviewed the article titled “Network Pharmacology-Based and Experimental Validation Elucidate the Target Mechanism of Vinorine in Ameliorating Secondary Brain Injury After Intracerebral Hemorrhage” by Wu et al. [<span>1</span>].</p><p>Through a combination of network pharmacology and in vitro/in vivo experiments, the authors propose that Vinorine (Vin) mitigates secondary damage following intracerebral hemorrhage by modulating the CXCR2–JAK–STAT pathway, downregulating MMP expression, and promoting neuronal survival. This study provides important clues regarding the potential of natural products in treating cerebral hemorrhage. We would like to offer some suggestions to further enhance the reliability and completeness of the research.</p><p>Firstly, intraperitoneal (ip) administration was employed in this study. While this route facilitates animal experimentation, the drug must first enter the central nervous system via the peripheral circulation. Peripheral metabolism and immune regulation may influence the assessment of direct central effects. In contrast, intrathecal, intracerebroventricular, or intrastriatal injection allows for more direct targeting of the lesion site [<span>2, 3</span>], thereby better facilitating the validation of Vin's central target effects; or intravenous injection, which is commonly used in clinical practice, also has certain advantages in terms of drug distribution and metabolism, and can provide a reference that is closer to clinical reality for the study. However, regardless of the new injection method used, appropriate toxicological validation should be conducted to ensure its safety and efficacy. Secondly, the authors observed that Vin can restore the integrity of the blood–brain barrier. CXCR2 is primarily expressed on neutrophils [<span>4</span>], which are known to disrupt the integrity of the blood–brain barrier through infiltration [<span>5</span>]. Although studies have shown that CXCR2 expression also increases during the activation of microglia [<span>6</span>], the authors did not perform immunofluorescence colocalization of CXCR2 with either microglia or neutrophils. Therefore, the reduction of CXCR2 expression by Vin may be achieved through the decrease of neutrophil infiltration. We propose that this effect may offer an alternative mechanism: BBB repair reduces the infiltration of peripheral immune cells—such as neutrophils—into brain parenchyma, thereby alleviating local inflammation [<span>7</span>]. This suggests that Vin's neuroprotective effects may not solely depend on regulating the JAK–STAT pathway in microglia, but also involve inhibiting the invasion of peripheral immune cells.</p><p>Therefore, subsequent studies may consider combining single-cell transcriptome sequencing with flow cytometry. By comparing the Vin-treated group with the vehicle control group, it could be interesting to analyze whether the ratio of neutrophils changes and to explore the potential effects o","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.70722","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mei Ma, Yue Tian, Ruiying Yin, Guangchan Jing, Mengren Zhang
Objective
Diabetes-associated cognitive dysfunction (DACD) is a prevalent and debilitating complication of diabetes, yet effective therapies remain limited. The traditional Chinese medicine compound Naofucong (NFC) has shown neuroprotective potential, but its underlying mechanisms are not fully understood. This study investigated the therapeutic efficacy and molecular mechanisms of NFC against DACD using an integrated multi-omics approach combined with experimental validation.
Methods
Streptozotocin-induced DACD rats received NFC (22.5 g/kg/day) for 12 weeks. Cognitive performance was assessed by the Morris water maze. Transcriptomics and untargeted metabolomics were integrated to identify key regulatory pathways, which were further validated using immunofluorescence, Golgi staining, cytokine profiling, qPCR, and western blotting.
Results
NFC significantly improved spatial learning and memory, attenuated neuronal damage in the hippocampus and cortex, and reduced pathological protein accumulation (APP, phosphorylated Tau). By integrating transcriptomics and metabolomics, we elucidated that NFC primarily acts via activation of the cAMP/PKA/CREB signaling pathway, leading to synaptic repair and neuroinflammatory modulation. Mechanistically, NFC restored synaptic ultrastructure, enhanced dendritic complexity and spine maturation, and upregulated neurotrophic factors (BDNF, NGF) and synaptic proteins (PSD-95, SYN). Furthermore, NFC inhibited glial overactivation, decreased pro-inflammatory cytokines (IL-1β, TNF-α, IFN-γ, IL-6, KC/GRO), and increased anti-inflammatory cytokines (IL-10, IL-13, IL-4), thereby re-establishing neuroimmune balance.
Conclusion
NFC exerts multi-target neuroprotective effects by activating the cAMP/PKA/CREB pathway and coordinately regulating synaptic plasticity and neuroinflammation. These findings highlight NFC as a promising candidate for DACD treatment.
{"title":"Multi-Target Mechanisms of the Naofucong in Ameliorating Diabetes-Associated Cognitive Dysfunction via cAMP/PKA/CREB-Mediated Synaptic and Inflammatory Regulation","authors":"Mei Ma, Yue Tian, Ruiying Yin, Guangchan Jing, Mengren Zhang","doi":"10.1002/cns.70716","DOIUrl":"10.1002/cns.70716","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Diabetes-associated cognitive dysfunction (DACD) is a prevalent and debilitating complication of diabetes, yet effective therapies remain limited. The traditional Chinese medicine compound Naofucong (NFC) has shown neuroprotective potential, but its underlying mechanisms are not fully understood. This study investigated the therapeutic efficacy and molecular mechanisms of NFC against DACD using an integrated multi-omics approach combined with experimental validation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Streptozotocin-induced DACD rats received NFC (22.5 g/kg/day) for 12 weeks. Cognitive performance was assessed by the Morris water maze. Transcriptomics and untargeted metabolomics were integrated to identify key regulatory pathways, which were further validated using immunofluorescence, Golgi staining, cytokine profiling, qPCR, and western blotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NFC significantly improved spatial learning and memory, attenuated neuronal damage in the hippocampus and cortex, and reduced pathological protein accumulation (APP, phosphorylated Tau). By integrating transcriptomics and metabolomics, we elucidated that NFC primarily acts via activation of the cAMP/PKA/CREB signaling pathway, leading to synaptic repair and neuroinflammatory modulation. Mechanistically, NFC restored synaptic ultrastructure, enhanced dendritic complexity and spine maturation, and upregulated neurotrophic factors (BDNF, NGF) and synaptic proteins (PSD-95, SYN). Furthermore, NFC inhibited glial overactivation, decreased pro-inflammatory cytokines (IL-1β, TNF-α, IFN-γ, IL-6, KC/GRO), and increased anti-inflammatory cytokines (IL-10, IL-13, IL-4), thereby re-establishing neuroimmune balance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>NFC exerts multi-target neuroprotective effects by activating the cAMP/PKA/CREB pathway and coordinately regulating synaptic plasticity and neuroinflammation. These findings highlight NFC as a promising candidate for DACD treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.70716","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div> <section> <h3> Aims</h3> <p>To investigate the role of the habenula (Hb)-centered brain network in regulating the cardiac autonomic nervous system (ANS) in subthreshold depression (StD), and to explore the brain–heart axis mechanisms underlying the antidepressant effects of heart rate variability biofeedback (HRV-BF) as a non-pharmacological intervention.</p> </section> <section> <h3> Methods</h3> <p>Thirty four StD participants and 32 healthy controls (HC) completed scale assessments (HAMD-17, PHQ-9, and PSQI) and cardiovascular measurements. StD participants received a 4-week HRV-BF with pre- and post-rs-BOLD fMRI. Bilateral Hb was used as the seed for ROI- and voxel-wise functional connectivity (FC) analyses. To minimize potential confounding effects of sex imbalance, only female participants were included in voxel-wise FC analysis (StD group, <i>n</i> = 8; HC group, <i>n</i> = 11) and pre-post intervention comparisons in ROI-wise FC analysis(StD group, <i>n</i> = 8).</p> </section> <section> <h3> Results</h3> <p>StD participants exhibited elevated heart rate, reduced HRV indices (lnRMSSD, HF power, lnSDNN), and increased LF power. ROI-wise FC analysis revealed that with increasing depression scores, z-transformed functional connectivity (zFC) value between the Hb and the nucleus accumbens (NAc), ventral pallidum (VeP), amygdala, globus pallidus internus (GPi), and substantia nigra (SN) shifted from positive to negative, indicating a transition from functional connectivity coupling to anti-coupling. Among these, Hb-NAc and Hb-VeP showed high discriminatory power (AUC = 0.876, <i>p</i> < 0.001). Voxel-wise FC analysis demonstrated weakened Hb functional connectivity with several key regions within the default mode network, salience network, central executive network, visual network, and sensorimotor network, including precuneus, right posterior cingulate cortex, left middle cingulate cortex, right superior parietal lobule, cuneus, right calcarine cortex, left superior occipital gyrus, right paracentral lobule, and right postcentral gyrus. A 4-week HRV-BF intervention improved HRV indices and partially restored the functional connectivity of Hb-centered networks, accompanied by significant improvements in depressive symptoms and sleep quality.</p> </section> <section> <h3> Conclusion</h3> <p>Aberrant Hb-centered functional connectivity may contribute to cardiac autonomic dysfunction in StD. Specifically, Hb-NAc and Hb-VeP functional connectivity may serve as neuroimaging biomarkers for StD. HRV-BF enhances vagal tone, rebalances cardiac A
{"title":"Heart Rate Variability Biofeedback Alleviates Subthreshold Depression by Reconstructing the Brain–Heart Axis via Habenular Network Functional Connectivity Modulation","authors":"Xiaodan Xu, Yingnan Cao, Guiping Lin, Zhiyuan Long, Xiaojun Ouyang, Chang Liu, Zhoulei Li, Tinghuai Wang","doi":"10.1002/cns.70692","DOIUrl":"10.1002/cns.70692","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To investigate the role of the habenula (Hb)-centered brain network in regulating the cardiac autonomic nervous system (ANS) in subthreshold depression (StD), and to explore the brain–heart axis mechanisms underlying the antidepressant effects of heart rate variability biofeedback (HRV-BF) as a non-pharmacological intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty four StD participants and 32 healthy controls (HC) completed scale assessments (HAMD-17, PHQ-9, and PSQI) and cardiovascular measurements. StD participants received a 4-week HRV-BF with pre- and post-rs-BOLD fMRI. Bilateral Hb was used as the seed for ROI- and voxel-wise functional connectivity (FC) analyses. To minimize potential confounding effects of sex imbalance, only female participants were included in voxel-wise FC analysis (StD group, <i>n</i> = 8; HC group, <i>n</i> = 11) and pre-post intervention comparisons in ROI-wise FC analysis(StD group, <i>n</i> = 8).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>StD participants exhibited elevated heart rate, reduced HRV indices (lnRMSSD, HF power, lnSDNN), and increased LF power. ROI-wise FC analysis revealed that with increasing depression scores, z-transformed functional connectivity (zFC) value between the Hb and the nucleus accumbens (NAc), ventral pallidum (VeP), amygdala, globus pallidus internus (GPi), and substantia nigra (SN) shifted from positive to negative, indicating a transition from functional connectivity coupling to anti-coupling. Among these, Hb-NAc and Hb-VeP showed high discriminatory power (AUC = 0.876, <i>p</i> < 0.001). Voxel-wise FC analysis demonstrated weakened Hb functional connectivity with several key regions within the default mode network, salience network, central executive network, visual network, and sensorimotor network, including precuneus, right posterior cingulate cortex, left middle cingulate cortex, right superior parietal lobule, cuneus, right calcarine cortex, left superior occipital gyrus, right paracentral lobule, and right postcentral gyrus. A 4-week HRV-BF intervention improved HRV indices and partially restored the functional connectivity of Hb-centered networks, accompanied by significant improvements in depressive symptoms and sleep quality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Aberrant Hb-centered functional connectivity may contribute to cardiac autonomic dysfunction in StD. Specifically, Hb-NAc and Hb-VeP functional connectivity may serve as neuroimaging biomarkers for StD. HRV-BF enhances vagal tone, rebalances cardiac A","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12720014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
W. Lv, Y. Ma, D. Li, et al., “Single-Cell RNA Sequencing and Spatial Transcriptomics Reveal a Novel Mechanism of Oligodendrocyte–Neuron Interaction in Cognitive Decline After High-Altitude Cerebral Edema,” CNS Neuroscience & Therapeutics 31, no. 6 (2025): e70485. https://doi.org/10.1111/cns.70485.
Notification was received after publication that the affiliation listed for the author Dazhi Guo was incomplete. The author, currently displayed as Dazhi Guo2, was requested to be listed as Dazhi Guo1,2
The correct affiliation information for this author is as follows: The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China, Department of Hyperbaric Oxygen, 6th Medical Center of PLA General Hospital, Beijing, China
{"title":"Correction to “Single-Cell RNA Sequencing and Spatial Transcriptomics Reveal a Novel Mechanism of Oligodendrocyte–Neuron Interaction in Cognitive Decline After High-Altitude Cerebral Edema”","authors":"","doi":"10.1002/cns.70723","DOIUrl":"10.1002/cns.70723","url":null,"abstract":"<p>W. Lv, Y. Ma, D. Li, et al., “Single-Cell RNA Sequencing and Spatial Transcriptomics Reveal a Novel Mechanism of Oligodendrocyte–Neuron Interaction in Cognitive Decline After High-Altitude Cerebral Edema,” CNS Neuroscience & Therapeutics 31, no. 6 (2025): e70485. https://doi.org/10.1111/cns.70485.</p><p>Notification was received after publication that the affiliation listed for the author Dazhi Guo was incomplete. The author, currently displayed as Dazhi Guo<sup>2</sup>, was requested to be listed as Dazhi Guo<sup>1,2</sup></p><p>The correct affiliation information for this author is as follows: The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China, Department of Hyperbaric Oxygen, 6th Medical Center of PLA General Hospital, Beijing, China</p><p>We apologize for this error.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12719796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Penny Ping Qin, Ivan Kin-Yeung Chak, Rebecca Lai-Di Kan, Min-Xia Jin, Bella Bing-Bing Zhang, Adam Wei-Li Xia, Tim Tian-Ze Lin, Sharie Xiao Wang, Jian-Hui Liu, Teris Cheung, Georg S. Kranz
Aims
We aimed to investigate the behavioral aftereffects of a novel noninvasive brain stimulation technique—transcranial pulse stimulation (TPS)—applied over the right motor cortex (rM1) in healthy adults.
Methods
Thirty-four healthy adults underwent a randomized, subject- and analyst- blind, crossover trial, receiving active TPS over the rM1 or control TPS over the vertex in two sessions 24 h apart. Motor performance was assessed using the Nine-Hole Peg Test (NHPT) and the Simple Reaction Time Task (SRTT) before, immediately after, and every 10 min for 40 min after each session. A linear mixed model and post hoc analyses were applied to evaluate the effects.
Results
No significant interaction effect (stimulation condition × time) was found. The left-hand NHPT performance significantly improved from 10 min post-TPS onward in both conditions (ps ≤ 0.002).
Conclusion
A single session of rM1-TPS does not yield significant improvements in motor dexterity compared to vertex-TPS. Future well-powered studies with a sham control condition and multiple stimulation sessions are needed to investigate the aftereffects using a combination of neurophysiological and neuroimaging approaches.
Trial Registration
This study was registered in ClinicalTrial.gov in April 2024 (NCT06312930)
{"title":"Effects of Transcranial Pulse Stimulation of the Primary Motor Cortex on Motor Performance in Healthy Adults: A Randomized Crossover Pilot Study","authors":"Penny Ping Qin, Ivan Kin-Yeung Chak, Rebecca Lai-Di Kan, Min-Xia Jin, Bella Bing-Bing Zhang, Adam Wei-Li Xia, Tim Tian-Ze Lin, Sharie Xiao Wang, Jian-Hui Liu, Teris Cheung, Georg S. Kranz","doi":"10.1002/cns.70711","DOIUrl":"10.1002/cns.70711","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We aimed to investigate the behavioral aftereffects of a novel noninvasive brain stimulation technique—transcranial pulse stimulation (TPS)—applied over the right motor cortex (rM1) in healthy adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty-four healthy adults underwent a randomized, subject- and analyst- blind, crossover trial, receiving active TPS over the rM1 or control TPS over the vertex in two sessions 24 h apart. Motor performance was assessed using the Nine-Hole Peg Test (NHPT) and the Simple Reaction Time Task (SRTT) before, immediately after, and every 10 min for 40 min after each session. A linear mixed model and post hoc analyses were applied to evaluate the effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No significant interaction effect (stimulation condition × time) was found. The left-hand NHPT performance significantly improved from 10 min post-TPS onward in both conditions (<i>p</i>s ≤ 0.002).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A single session of rM1-TPS does not yield significant improvements in motor dexterity compared to vertex-TPS. Future well-powered studies with a sham control condition and multiple stimulation sessions are needed to investigate the aftereffects using a combination of neurophysiological and neuroimaging approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>This study was registered in ClinicalTrial.gov in April 2024 (NCT06312930)</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12717462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Substance use disorder (SUD) is a complex, chronic, and relapsing encephalopathy associated with inflammatory processes. This study aims to conduct a bibliometric analysis to elucidate the current landscape, research hotspots, and evolving trends in the field of SUD-related inflammation imbalance.
Methods
Original research and review articles pertaining to “SUD-inflammation” subject were systematically retrieved from the Web of Science Core Collection (WoSCC) database, encompassing publications from its inception to January 1, 2025. Co-authorship, collaboration, co-citation, and co-occurrence analyses were performed using VOSviewer, and CiteSpace was utilized to identify strongest citation bursts and keyword trends.
Results
A total of 2318 publications on “SUD-inflammation” realm were included. A marked increase in publication output was observed starting in 2019. The United States (US) and China emerged as the most prolific countries. The journal, institution, and author, with the largest number of total publications (NP), were respectively JOURNAL OF ETHNOPHARMACOLOGY, UNIVERSITY OF CALIFORNIA SYSTEM, and Michael Maes. Core terms “microglial activation,” “oxidative stress,” and “TLR4 signaling” were among the most frequently studied topics. Additionally, the roles of the “gut-immune-brain” axis and N-acetylcysteine in drug addiction have been receiving significant attention.
Conclusion
This bibliometric study delineates the foundational knowledge structural and mapping of the “SUD-inflammation” field over the past 25 years. The findings provide a comprehensive and data-driven perspective on the evolving research landscape, offering valuable insights for future investigations and resource allocation.
背景：物质使用障碍（SUD）是一种复杂的、慢性的、反复发作的与炎症过程相关的脑病。本研究旨在通过文献计量学分析，阐明sud相关炎症失衡领域的现状、研究热点和发展趋势。方法：系统地从Web of Science Core Collection （WoSCC）数据库中检索与“SUD-inflammation”主题相关的原始研究和综述文章，包括从该数据库建立到2025年1月1日的出版物。使用VOSviewer进行合著、协作、共被引和共现分析，并使用CiteSpace识别最强引文爆发和关键词趋势。结果：共纳入“SUD-inflammation”领域的文献2318篇。2019年以来，出版物产量显著增长。美国和中国成为最多产的国家。发表论文总数最多的期刊、机构和作者分别是journal of ETHNOPHARMACOLOGY、UNIVERSITY of CALIFORNIA SYSTEM和Michael Maes。核心术语“小胶质细胞激活”、“氧化应激”和“TLR4信号传导”是最常被研究的主题。此外，“肠-免疫-脑”轴和n -乙酰半胱氨酸在药物成瘾中的作用已受到重视。结论：本文献计量学研究描述了过去25年来“sud -炎症”领域的基本知识结构和图谱。这些发现为不断发展的研究格局提供了一个全面和数据驱动的视角，为未来的调查和资源分配提供了有价值的见解。
{"title":"Worldwide Research Trends on Substance Use Disorder-Related Inflammatory Imbalances: A Bibliometric Analysis","authors":"Shirui Cao, Longtao Yang, Ruixin Wang, Jun Liu","doi":"10.1002/cns.70719","DOIUrl":"10.1002/cns.70719","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Substance use disorder (SUD) is a complex, chronic, and relapsing encephalopathy associated with inflammatory processes. This study aims to conduct a bibliometric analysis to elucidate the current landscape, research hotspots, and evolving trends in the field of SUD-related inflammation imbalance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Original research and review articles pertaining to “SUD-inflammation” subject were systematically retrieved from the Web of Science Core Collection (WoSCC) database, encompassing publications from its inception to January 1, 2025. Co-authorship, collaboration, co-citation, and co-occurrence analyses were performed using VOSviewer, and CiteSpace was utilized to identify strongest citation bursts and keyword trends.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 2318 publications on “SUD-inflammation” realm were included. A marked increase in publication output was observed starting in 2019. The United States (US) and China emerged as the most prolific countries. The journal, institution, and author, with the largest number of total publications (NP), were respectively JOURNAL OF ETHNOPHARMACOLOGY, UNIVERSITY OF CALIFORNIA SYSTEM, and Michael Maes. Core terms “microglial activation,” “oxidative stress,” and “TLR4 signaling” were among the most frequently studied topics. Additionally, the roles of the “gut-immune-brain” axis and N-acetylcysteine in drug addiction have been receiving significant attention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This bibliometric study delineates the foundational knowledge structural and mapping of the “SUD-inflammation” field over the past 25 years. The findings provide a comprehensive and data-driven perspective on the evolving research landscape, offering valuable insights for future investigations and resource allocation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12717472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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