Brain Research Bulletin最新文献

{"title":"CAF-derived exosomes promote the proliferation and invasion of pituitary adenoma cells via miR-184 transfer","authors":"Qiu Du ,&nbsp;Zhiyong Chen ,&nbsp;Weiyu Zhang ,&nbsp;Mengchao Zhu ,&nbsp;Zhichao Yang ,&nbsp;Yaru Li ,&nbsp;Lei Xu ,&nbsp;Jianmin Zhang ,&nbsp;Aijun Peng ,&nbsp;Qingling Feng","doi":"10.1016/j.brainresbull.2025.111678","DOIUrl":"10.1016/j.brainresbull.2025.111678","url":null,"abstract":"<div><div>Pituitary adenomas (PAs) are common intracranial tumors whose mass effects and endocrine dysfunction pose serious threats to patient health. However, the mechanisms underlying their progression, particularly the role of the tumor microenvironment (TME), remain insufficiently studied. Within this context, cancer-associated fibroblasts (CAFs) have been shown to drive tumor development via extracellular matrix remodeling and extracellular vesicle release, but their specific contributions to PA progression remain unclear. In this study, we observed a correlation between PA invasiveness and fibroblast density in the TME. Functionally, both CAFs and CAF-derived exosomes significantly enhanced the proliferation and invasion of PA cells compared to normal fibroblasts. Small RNA sequencing identified 16 upregulated and 8 downregulated miRNAs in CAF-derived exosomes, with KEGG analysis indicating enrichment in MAPK signaling, regulation of actin cytoskeleton, and lysosome-related pathways. Among these, miR-184 was notably upregulated in both CAF-derived exosomes and PA specimens. We further demonstrated that exosomal miR-184 from CAFs could be transferred into PA cells, promoting their proliferation and invasion, while miR-184 knockdown attenuated the tumor-promoting effects of CAF-derived exosomes. Mechanistically, TLE1 was validated as a direct functional target of miR-184. In summary, our study reveals exosomal miR-184 as a key mediator of CAF-driven PA progression, highlighting its potential as a therapeutic target for PAs.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111678"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The pulvinar nucleus and its role in cognitive functions","authors":"Nelson Cortes,&nbsp;Capucine Mandel,&nbsp;Lamyae Ikan,&nbsp;Christian Casanova","doi":"10.1016/j.brainresbull.2025.111672","DOIUrl":"10.1016/j.brainresbull.2025.111672","url":null,"abstract":"<div><div>The pulvinar is a higher-order thalamic hub with widespread cortico-cortical and cortico-limbic connectivity. Here we synthesize evidence that pulvinar circuits shape perception and cognition via three computations: (i) precision-weighted gain for routing information across visual hierarchies, (ii) priority mapping that supports selection of behaviorally relevant stimuli, and (iii) temporal alignment that facilitates feature binding and multisensory integration. We summarize lesion, inactivation and imaging studies linking these operations to attention, sensory gain, and socio-emotional processing. We then review pulvinar-related alterations across neuropsychiatric conditions (e.g., schizophrenia, autism spectrum disorder, major depressive disorder, anxiety), focusing on convergent patterns of thalamo-cortical reconfiguration rather than disorder-general clinical descriptions. Finally, we integrate these findings with contemporary frameworks (predictive coding; distributed global workspace; constructionist theory of emotions), outlining testable predictions about frequency-specific coupling and state-dependent routing between occipito-temporal, fronto-parietal and limbic networks. This concise account situates the pulvinar as a modulatory hub that can influence both sensory and affective dimensions of cognition, and highlights priorities for causal human and animal work.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111672"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145683996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shen-Xiong-Tong-Mai granule suppresses nerve cell apoptosis to ameliorate ischemic stroke via activating PI3K/Akt signaling pathway","authors":"Fang Yang ,&nbsp;Yujia Zhong ,&nbsp;Xuhong Yang ,&nbsp;Weihong Li ,&nbsp;Yang Zhang","doi":"10.1016/j.brainresbull.2025.111694","DOIUrl":"10.1016/j.brainresbull.2025.111694","url":null,"abstract":"<div><h3>Background</h3><div>Ischemic stroke (IS) is a common subtype of stroke in China, accounting for 60 %-80 % of all stroke cases. Shen-Xiong-Tong-Mai granule (SXTMG) is one of the commonly used herbal medicine formulas in TCM. The present work aimed to explore the predominant active substances and molecular mechanisms underlying SXTMG against IS.</div></div><div><h3>Methods</h3><div>IS animal model and cell model were constructed using middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) methods, respectively. The SXTMG and IS targets were predicted using four databases. UPLC/MS analysis was employed to identify the active compounds of SXTMG. The pathway changes were detected using western blot and immunofluorescence staining.</div></div><div><h3>Results</h3><div>Firstly, SXTMG significantly reduced the ischemic area, brain edema, and nerve function injury of MCAO rats, exhibiting crucial anti-IS effects. Totally 22 active compounds were identified in SXTMG based on HPLC-MS/MS results. After bioinformatics analysis, 89 common targets were identified, which were significantly enriched in pathways including apoptosis pathway and PI3K/Akt signaling. Finally, in vitro experiments indicated that SXTMG treatment significantly inhibited the OGD/R HT22 cell apoptosis and activated the PI3K/Akt signaling in OGD/R HT22 cells.</div></div><div><h3>Conclusion</h3><div>SXTMG possessed promising protective effects against IS through triggering PI3K/Akt signaling to suppress nerve cell apoptosis.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111694"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hippocampal-amygdala subregional characteristic changes predict heterogeneous post-chemotherapy neuropsychological outcomes","authors":"Jiahui Zheng ,&nbsp;Xiaoyu Zhou ,&nbsp;Jing Yang ,&nbsp;Lin Tang ,&nbsp;Yu Tang ,&nbsp;Jing Zhang ,&nbsp;Yong Tan ,&nbsp;Hong Yu ,&nbsp;Xunrong Luo ,&nbsp;Meng Lin ,&nbsp;Daihong Liu ,&nbsp;Jiuquan Zhang","doi":"10.1016/j.brainresbull.2025.111713","DOIUrl":"10.1016/j.brainresbull.2025.111713","url":null,"abstract":"<div><h3>Background</h3><div>The hippocampus and amygdala are interconnected structures critical for cognition. Existing whole-region analyses show inconsistent findings, while subregional changes and their interactions remain unclear. Therefore, we aim to investigate subregional abnormalities in breast cancer patients undergoing neoadjuvant chemotherapy, focusing on both regional and network-level alterations.</div></div><div><h3>Methods</h3><div>A total of 79 breast cancer (BC) patients and 98 healthy controls (HC) were enrolled in our study. The subregional volumes and network measures in BC patients were analyzed at three time points: baseline (B0), following the first cycle of neoadjuvant chemotherapy (NAC) (B1), and at the completion of therapy (B2). These were then compared with those of the HC group at B0. Partial Least Squares Regression (PLSR) identified subregional predictors of chemotherapy-related cognitive dysfunction.</div></div><div><h3>Results</h3><div>Subregional analysis disclosed significant volume disparities in four hippocampal subregions and one amygdala subregion among BC patients across three time points. Compared to B0, 80 % of these regions exhibited volume increases, and 80 % of these differences were statistically significant during the B1. Network analysis demonstrated significant differences in the nodal measures of the Subregion Interconnected Networks in three hippocampal subregions and one amygdalar subregion across the three time points. Notably, all these subregions are located in the right hemisphere, displaying a lateralized distribution pattern. Eleven PLSR models for multidomain cognitive functions demonstrated predictive validity, identifying key subregions as cognitive impairment biomarkers.</div></div><div><h3>Conclusion</h3><div>Chemotherapy induces distinct hippocampal-amygdalar subregional volumetric changes, which possess predictive significance for chemotherapy-related multidomain cognitive impairment in BC patients.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111713"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral CD200R signaling: A critical regulator of post-stroke inflammation in aged mice","authors":"Conelius Ngwa,&nbsp;Afzal Misrani,&nbsp;Yan Xu,&nbsp;Jingjing Wang,&nbsp;Rodney Ritzel,&nbsp;Fudong Liu","doi":"10.1016/j.brainresbull.2025.111686","DOIUrl":"10.1016/j.brainresbull.2025.111686","url":null,"abstract":"<div><div>The immune responses to ischemic stroke are subjected to endogenous inhibitory pathways that delimitate the post-stroke inflammation. Among them, the interaction between CD200 and its receptor (CD200R) is increasingly recognized for its role in regulating neuroinflammation across various central nervous system (CNS) disorders. In the present study, we have examined the role of central (brain) vs. peripheral CD200R signaling in acute ischemic stroke using aged bone marrow chimeric (BMC) mice (16–19 months old). These chimeras were generated by transplanting bone marrow from CD200R knockout (KO), green fluorescent protein (GFP), or wild-type (WT) donor mice into irradiated recipient mice, and then subjected to a 45-min transient middle cerebral artery occlusion (MCAO). At three days post-stroke, flow cytometry, ELISA, and immunohistochemistry (IHC) were used to assess immune responses. Infarct volumes and neurobehavioral deficits were also evaluated. We found that T cell infiltration into the brain was significantly greater in KO-to-GFP (central CD200R signaling) compared to GFP-to-KO (peripheral CD200R signaling) mice. KO-to-GFP mice also exhibited significantly higher levels of pro-inflammatory cytokines IL-1β and TNF-α in the ischemic brain than GFP-to-KO chimeras. Correspondingly, KO-to-GFP mice showed significantly larger brain infarct volumes and worse neurobehavior deficits compared to GFP-to-KO chimeras. Together, these findings indicate that the peripheral (not the central) CD200R signaling plays a critical role in controlling post-stroke immune responses and delineating ischemic injury.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111686"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyamine pathway in neurological disorders: Potential therapeutic implications based on current evidences","authors":"Mengqi Yan ,&nbsp;Yingying Tang ,&nbsp;Shuo Zhang ,&nbsp;Li Yu ,&nbsp;Cenglin Xu","doi":"10.1016/j.brainresbull.2025.111711","DOIUrl":"10.1016/j.brainresbull.2025.111711","url":null,"abstract":"<div><div>Polyamines (PAs) with a positive charge and low molecular weight, are a class of general biogenic amines that are involved in many important cellular processes, including maintaining nucleic acid stability, controlling ion channel activity, regulating transcription and translation, modulating cell cycle, influencing kinase activity, protecting oxidative damage, and maintaining membrane structure. Cumulative studies have shown that in various neurological disorders, the normal synthesis and metabolism of the polyamine pathway would be disrupted. And the changed polyamine system is believed to participate in the pathophysiological process of the disease through various mechanisms, these include down-regulating or up-regulating PA, putrescine, spermidine, spermine, the key enzymes in the polyamine catabolic pathway include ornithine decarboxylase (ODC), spermidine/spermine N1-acetyltransferase (SAT1), and spermine oxidase (SMOX). They also play a role in the disease process by affecting different downstream molecular pathways or mechanisms, resulting in distinct changes under different disease conditions. With such implications of polyamine in the disorder process, targeting the synthesis and metabolism of polyamine system emerges as potential approaches for intervening the neurological disorders. We attempted to explore the potential molecular mechanisms and molecular connections involved in polyamines at first. Then, we describe possible links between polyamines and various neurological disorders, and finally the possible therapeutic implications on targeting the polyamine system for the treatment of various disorders were proposed. This review may provide an up-to-date overview to propose the new perspective about targeting PA for developing potential therapeutic strategies.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111711"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease-specific network pattern of perinatal depression revealed by Common Orthogonal Basis Extraction","authors":"Yueheng Peng ,&nbsp;Jihan Wang ,&nbsp;Xianyong Fan ,&nbsp;Yue Yu ,&nbsp;Guolin He ,&nbsp;Dawazhuoma ,&nbsp;Lu Jiang ,&nbsp;Tingting Zhang ,&nbsp;Silangquncuo ,&nbsp;Chanlin Yi ,&nbsp;Dezhong Yao ,&nbsp;Bin Lv ,&nbsp;Peng Xu ,&nbsp;Kaibo Shi","doi":"10.1016/j.brainresbull.2026.111719","DOIUrl":"10.1016/j.brainresbull.2026.111719","url":null,"abstract":"<div><div>The clinical diagnosis of perinatal depression (PD) presents considerable challenge, as it is much harder to identify than non-perinatal depression. Psychologically, common emotional fluctuations during pregnancy are easily confounded with depressive symptoms, leading to missed and incorrect diagnoses. Neurologically, pregnancy-induced alterations in brain activity could obscure neuroimaging features specific to PD. Therefore, this study introduced an innovative approach that combined brain network analysis with Common Orthogonal Basis Extraction (COBE) to identify a <em>PD-Specific Network Pattern</em> from resting-state brain networks, as well as validating its efficacy in diagnosis and assessment. Resting-state electroencephalography (EEG) data were collected from 21 patients with PD and 20 healthy pregnant (HP) individuals, from which functional brain networks were constructed. An optimized COBE method was then employed to extract <em>Exclusive Network Pattern</em> for each group, as well as <em>Common Network Pattern</em> shared by all participants (PD + HP). This process enabled the identification of the PD-Specific Network Pattern that most consistent with neural mechanisms of PD. Based on the PD-Specific Network Pattern, <em>PD-Specific Features</em> were derived and applied to train support vector machine and multiple linear regression models, which respectively performed individual-level classification and assessment. This study effectively addressed the limitation of traditional neuroimaging techniques in the diagnosis of PD, providing a new avenue for objective screening and dynamic monitoring of perinatal depression.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111719"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain network localization of high-frequency heart rate variability: A meta-analysis and coordinate-based network mapping approach","authors":"Yifan Fang ,&nbsp;Tianyi Li ,&nbsp;Wenwen Liang,&nbsp;Qing Du,&nbsp;Chensheng Pan,&nbsp;Zhou Zhu","doi":"10.1016/j.brainresbull.2025.111673","DOIUrl":"10.1016/j.brainresbull.2025.111673","url":null,"abstract":"<div><div>This study investigated the neural mechanisms behind high-frequency heart rate variability (HF-HRV), a marker of cardiac parasympathetic tone, which is crucial for understanding the interplay between physiological and emotional regulation. Previous neuroimaging studies have yielded inconsistent results, making it challenging to identify the specific brain networks involved in cardiac vagal control. To address this issue, we conducted a systematic search of PubMed, Web of Science, and Scopus for studies linking HF-HRV with brain activation coordinates. An Activation Likelihood Estimation (ALE) meta-analysis was performed to identify convergence in brain activation associated with HF-HRV. We subsequently used coordinate-based network mapping to investigate the functional connectivity of brain regions related to HF-HRV, via a database of resting-state functional connectivity from 1000 healthy volunteers. Despite the high heterogeneity among studies, which prevented the ALE meta-analysis from identifying significant voxels or clusters, coordinate-based network mapping revealed consistent network overlap in the subgenual anterior cingulate cortex (sgACC) and ventromedial prefrontal cortex (vmPFC), both of which were positively correlated with HF-HRV. No significantly correlated areas were detected in the brain networks that were negatively correlated with HF-HRV. These findings suggest that HF-HRV is associated with a distributed network of brain regions, with the sgACC and the vmPFC playing crucial roles in cardiac vagal control. This study introduces an innovative approach to understanding the role of the brain in HF-HRV control and provides a foundation for future research into the neural mechanisms underlying cardiac autonomic regulation.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111673"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145683995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural damage and inflammation in myotonic dystrophy type 1: Longitudinal analysis of serum NFL, GFAP, and IL-6","authors":"Joana Garmendia ,&nbsp;Garazi Labayru ,&nbsp;Ainhoa Alberro ,&nbsp;Laura Martins-Almeida ,&nbsp;David Otaegui ,&nbsp;Pablo Iruzubieta ,&nbsp;Adolfo Lopez de Munain ,&nbsp;Andone Sistiaga","doi":"10.1016/j.brainresbull.2025.111688","DOIUrl":"10.1016/j.brainresbull.2025.111688","url":null,"abstract":"<div><h3>Introduction</h3><div>Myotonic dystrophy type 1 (DM1) is a progressive, multisystemic disease affecting the central nervous system (CNS). Blood-based biomarkers such as neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and interleukin-6 (IL-6) offer potential as non-invasive indicators of CNS dysfunction and/or inflammation. However, their longitudinal dynamics and clinical relevance in DM1 remain unclear. Additionally, sex-related differences in these biomarkers are poorly understood. This study aimed to investigate NFL, GFAP, and IL-6 serum levels in patients with DM1, examine sex-differences, track changes over four years, and explore associations with genetic, muscular, cognitive, and neuroimaging outcomes.</div></div><div><h3>Method</h3><div>Retrospective data from 70 DM1 patients and 54 healthy controls (HC) were analyzed. Longitudinal data were available for 68 participants (39 DM1, 29 HC). Biomarkers were measured using the ELLA immunoassay. DM1 patients had data on genetic, muscular, cognitive and structural brain outcomes. Analyses were adjusted for age.</div></div><div><h3>Results</h3><div>NFL and IL-6 levels were significantly higher in DM1 patients compared to HC, while GFAP levels did not differ. Male DM1 patients exhibited higher NFL and IL-6 levels compared to females. No significant longitudinal changes were observed over a four-year period. NFL and IL-6 levels correlated with larger genetic expansions and poorer cognitive performance.</div></div><div><h3>Discussion</h3><div>NFL and IL-6 may reflect neural damage and systemic inflammation in DM1 and could serve as biomarkers of cognitive dysfunction. However, their limited longitudinal sensitivity suggests longer follow-up is needed to evaluate their utility for disease monitoring.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111688"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AD16 as a novel therapeutic agent: Mechanisms and efficacy in chronic inflammatory pain management","authors":"Zhi-Ping Hu ,&nbsp;Hai-Juan Ma ,&nbsp;Hui Liu ,&nbsp;Zhi-Xian He ,&nbsp;Dan-Dan Jia ,&nbsp;Ya-Lan Sun ,&nbsp;Zhi-Hua Huang ,&nbsp;Zhi-dong Yuan ,&nbsp;Tao Chen ,&nbsp;Cheng Huang","doi":"10.1016/j.brainresbull.2025.111707","DOIUrl":"10.1016/j.brainresbull.2025.111707","url":null,"abstract":"<div><div>Chronic inflammatory pain is a complex condition marked by enduring pain due to inflammation and central sensitization. Present therapeutic strategies primarily rely on non-steroidal anti-inflammatory drugs (NSAIDs) or opioid-based treatments, which frequently entail considerable adverse effects and demonstrate limited efficacy in managing chronic pain. Therefore, there is a pressing need to identify novel therapeutic strategies that can effectively target and modulate the underlying mechanisms of chronic inflammatory pain. Here, we examined an innovation compound named AD16 in mitigating chronic inflammatory pain and investigated its molecular mechanisms. The findings revealed that AD16 significantly attenuated pain-related behaviors in rat models of chronic inflammatory pain induced by complete Freund's adjuvant (CFA), specifically reducing foot swelling and mechanical allodynia. AD16 was found to be associated with the activation of GABA_B receptors and alterations in the expression ratios of GluN2A/GluN2B subunits, suggesting a potential impact on synaptic plasticity. Furthermore, AD16 was correlated with a reduction in systemic inflammatory markers, as demonstrated by decreased levels of IL-1β and increased levels of IL-10 known to play roles in the modulation of central sensitization in inflammatory pain. These findings suggest that AD16 may counteract CFA-induced central sensitization by restoring two critical pathways: (1) the balance between neuronal excitation and inhibition, and (2) the equilibrium between pro-inflammatory and anti-inflammatory immune responses within the spinal cord. Consequently, AD16 represents a promising therapeutic candidate for chronic inflammatory pain.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111707"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}