Pub Date : 2025-03-13DOI: 10.1016/j.brainresbull.2025.111302
Xiaolei Song , Fengzhu Zhang , Danyu Han , Jingzhe Yu , Qian Ren , Xiaoming Xin , Rongliang Guo , Weidong Le
The striatum, a critical component of the basal ganglia, is essential for motor control, cognitive processing, and emotional regulation. Medium spiny neurons (MSNs) are the primary neuronal population in the striatum, classified into D1 and D2 subtypes. The transcription factor Pou3f1 has been hypothesized to play a crucial role in the development of pyramidal neurons. Recently, a comprehensive analysis of the human embryonic scRNA-seq dataset predicted and emphasized the bridging function of POU3F1 between striatal progenitor cells and immature neurons, though this finding lacked genetic validation. In this study, we found that Pou3f1 expression was significantly reduced after Six3 deletion. However, Pou3f1 deletion does not significantly affect the number or subtype composition of MSNs, nor the proliferation and differentiation of progenitor cells, in our Pou3f1 conditional knockout (cko) mice, challenging the in silico predictions based on human data. These results suggest that Pou3f1 is not required for the specification, generation, or differentiation of MSNs, though its potential involvement in other aspects of striatal development cannot be entirely ruled out.
{"title":"Reevaluating the role of Pou3f1 in striatal development: Evidence from transgenic mouse models","authors":"Xiaolei Song , Fengzhu Zhang , Danyu Han , Jingzhe Yu , Qian Ren , Xiaoming Xin , Rongliang Guo , Weidong Le","doi":"10.1016/j.brainresbull.2025.111302","DOIUrl":"10.1016/j.brainresbull.2025.111302","url":null,"abstract":"<div><div>The striatum, a critical component of the basal ganglia, is essential for motor control, cognitive processing, and emotional regulation. Medium spiny neurons (MSNs) are the primary neuronal population in the striatum, classified into D1 and D2 subtypes. The transcription factor <em>Pou3f1</em> has been hypothesized to play a crucial role in the development of pyramidal neurons. Recently, a comprehensive analysis of the human embryonic scRNA-seq dataset predicted and emphasized the bridging function of <em>POU3F1</em> between striatal progenitor cells and immature neurons, though this finding lacked genetic validation. In this study, we found that <em>Pou3f1</em> expression was significantly reduced after <em>Six3</em> deletion. However, <em>Pou3f1</em> deletion does not significantly affect the number or subtype composition of MSNs, nor the proliferation and differentiation of progenitor cells, in our <em>Pou3f1</em> conditional knockout (cko) mice, challenging the <em>in silico</em> predictions based on human data. These results suggest that <em>Pou3f1</em> is not required for the specification, generation, or differentiation of MSNs, though its potential involvement in other aspects of striatal development cannot be entirely ruled out.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111302"},"PeriodicalIF":3.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-12DOI: 10.1016/j.brainresbull.2025.111297
Marina E. Emborg , Jeanette M. Metzger , Kevin D’Amour , Julia C. Colwell , Lindsey C. Neumann , Ai Zhang , Howard J. Federoff
Intracerebral grafting of dopamine-producing cells is proposed as a strategy to replace the typical neurons lost to Parkinson’s disease (PD) and improve PD motor symptoms. Non-human primate studies have provided clues on the relationship between the host’s immune response and grafting success. Herein, we discuss how the host’s immune system differentially affects the graft depending on the origin of the cells and reflect on the advantages and limitations of the immune paradigms utilized to assess graft-related outcomes. We also consider new strategies to minimize or circumvent the host’s immunological response and related preclinical research needed to identify the most promising new approaches to be translated into the clinic.
{"title":"Advantages and challenges of using allogeneic vs. autologous sources for neuronal cell replacement in Parkinson’s disease: Insights from non-human primate studies","authors":"Marina E. Emborg , Jeanette M. Metzger , Kevin D’Amour , Julia C. Colwell , Lindsey C. Neumann , Ai Zhang , Howard J. Federoff","doi":"10.1016/j.brainresbull.2025.111297","DOIUrl":"10.1016/j.brainresbull.2025.111297","url":null,"abstract":"<div><div>Intracerebral grafting of dopamine-producing cells is proposed as a strategy to replace the typical neurons lost to Parkinson’s disease (PD) and improve PD motor symptoms. Non-human primate studies have provided clues on the relationship between the host’s immune response and grafting success. Herein, we discuss how the host’s immune system differentially affects the graft depending on the origin of the cells and reflect on the advantages and limitations of the immune paradigms utilized to assess graft-related outcomes. We also consider new strategies to minimize or circumvent the host’s immunological response and related preclinical research needed to identify the most promising new approaches to be translated into the clinic.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111297"},"PeriodicalIF":3.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-12DOI: 10.1016/j.brainresbull.2025.111298
Fangzhou Xu , Yitai Lou , Yunqing Deng , Zhixiao Lun , Pengcheng Zhao , Di Yan , Zhe Han , Zhirui Wu , Chao Feng , Lei Chen , Jiancai Leng
Traditional machine learning methods struggle with efficiency when processing large-scale data, while deep learning approaches, such as convolutional neural networks (CNN) and long short-term memory networks (LSTM), exhibit certain limitations when handling long-duration sequences. The choice of convolutional kernel size needs to be determined after several experiments, and LSTM has difficulty capturing effective information from long-time sequences. In this paper, we propose a transfer learning (TL) method based on Transformer, which constructs a new network architecture for feature extraction and classification of electroencephalogram (EEG) signals in the time-space domain, named TS-former. The frequency and spatial domain information of EEG signals is extracted using the Filter Bank Common Spatial Pattern (FBCSP), and the resulting features are subsequently processed by the Transformer to capture temporal patterns. The input features are processed by the Transformer using a multi-head attention mechanism, and the final classification outputs are generated through a fully connected layer. A classification model is pre-trained using fine-tuning techniques. When performing a new classification task, only some layers of the model are modified to adapt it to the new data and achieve good classification results. The experiments are conducted on a motor imagery (MI) EEG dataset from 16 spinal cord injury (SCI) patients. After training the model using a ten-time ten-fold cross-validation method, the average classification accuracy reached 95.09 %. Our experimental results confirm a new approach to build a brain-computer interface (BCI) system for rehabilitation training of SCI patients.
{"title":"Motor imagery EEG decoding based on TS-former for spinal cord injury patients","authors":"Fangzhou Xu , Yitai Lou , Yunqing Deng , Zhixiao Lun , Pengcheng Zhao , Di Yan , Zhe Han , Zhirui Wu , Chao Feng , Lei Chen , Jiancai Leng","doi":"10.1016/j.brainresbull.2025.111298","DOIUrl":"10.1016/j.brainresbull.2025.111298","url":null,"abstract":"<div><div>Traditional machine learning methods struggle with efficiency when processing large-scale data, while deep learning approaches, such as convolutional neural networks (CNN) and long short-term memory networks (LSTM), exhibit certain limitations when handling long-duration sequences. The choice of convolutional kernel size needs to be determined after several experiments, and LSTM has difficulty capturing effective information from long-time sequences. In this paper, we propose a transfer learning (TL) method based on Transformer, which constructs a new network architecture for feature extraction and classification of electroencephalogram (EEG) signals in the time-space domain, named TS-former. The frequency and spatial domain information of EEG signals is extracted using the Filter Bank Common Spatial Pattern (FBCSP), and the resulting features are subsequently processed by the Transformer to capture temporal patterns. The input features are processed by the Transformer using a multi-head attention mechanism, and the final classification outputs are generated through a fully connected layer. A classification model is pre-trained using fine-tuning techniques. When performing a new classification task, only some layers of the model are modified to adapt it to the new data and achieve good classification results. The experiments are conducted on a motor imagery (MI) EEG dataset from 16 spinal cord injury (SCI) patients. After training the model using a ten-time ten-fold cross-validation method, the average classification accuracy reached 95.09 %. Our experimental results confirm a new approach to build a brain-computer interface (BCI) system for rehabilitation training of SCI patients.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111298"},"PeriodicalIF":3.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-12DOI: 10.1016/j.brainresbull.2025.111300
Saúl Sal-Sarria , Isabel López-Taboada , Héctor González-Pardo , Andrea Fernández-Blanco , Nélida M. Conejo
The global rise in obesity and poor dietary habits, particularly the consumption of high-fat, high-sucrose (HFS) diets, is a growing public health concern. These diets, especially when consumed during critical developmental periods, such as gestation and early life, are linked to long-term consequences on both physical and mental health. Early exposure to obesogenic diets has been shown to disrupts brain function and increases the risk of anxiety, depression, and additional emotional disorders. However, it has been suggested that dietary changes during early life may reverse these effects. This study investigated whether switching from an HFS diet to a standard diet (SD) after weaning could reverse abnormal emotional responses (o anxiety- and depression-like behavior) and brain energy metabolic capacity in rats.
Male and female Wistar rats were divided into three groups: one on continuous SD, one on an HFS diet from gestation until adulthood, and one that shifted from HFS to SD after weaning. Emotional behavior was assessed using the saccharin preference test, forced swimming test, and elevated zero maze test. Brain metabolism was evaluated by measuring cytochrome c oxidase (CCO) activity in key regions involved in emotion regulation, such as the nucleus accumbens, ventral pallidum, dorsal striatum, and the bed nucleus of stria terminalis.
Adult animals exposed to the HFS diet exhibited increased depression and anxiety-like behaviors, and elevated CCO activity. Notably, sex differences were observed, with males showing more pronounced anxiety- and depression-like behaviors, although both sexes improved after diet switching. These findings suggest that early dietary interventions can mitigate diet-induced emotional and metabolic disturbances, thereby underscoring the importance of nutrition during critical developmental periods.
{"title":"Reversing the impact of an obesogenic diet on emotion regulation and brain metabolism: A rat model study","authors":"Saúl Sal-Sarria , Isabel López-Taboada , Héctor González-Pardo , Andrea Fernández-Blanco , Nélida M. Conejo","doi":"10.1016/j.brainresbull.2025.111300","DOIUrl":"10.1016/j.brainresbull.2025.111300","url":null,"abstract":"<div><div>The global rise in obesity and poor dietary habits, particularly the consumption of high-fat, high-sucrose (HFS) diets, is a growing public health concern. These diets, especially when consumed during critical developmental periods, such as gestation and early life, are linked to long-term consequences on both physical and mental health. Early exposure to obesogenic diets has been shown to disrupts brain function and increases the risk of anxiety, depression, and additional emotional disorders. However, it has been suggested that dietary changes during early life may reverse these effects. This study investigated whether switching from an HFS diet to a standard diet (SD) after weaning could reverse abnormal emotional responses (o anxiety- and depression-like behavior) and brain energy metabolic capacity in rats.</div><div>Male and female Wistar rats were divided into three groups: one on continuous SD, one on an HFS diet from gestation until adulthood, and one that shifted from HFS to SD after weaning. Emotional behavior was assessed using the saccharin preference test, forced swimming test, and elevated zero maze test. Brain metabolism was evaluated by measuring cytochrome c oxidase (CCO) activity in key regions involved in emotion regulation, such as the nucleus accumbens, ventral pallidum, dorsal striatum, and the bed nucleus of stria terminalis.</div><div>Adult animals exposed to the HFS diet exhibited increased depression and anxiety-like behaviors, and elevated CCO activity. Notably, sex differences were observed, with males showing more pronounced anxiety- and depression-like behaviors, although both sexes improved after diet switching. These findings suggest that early dietary interventions can mitigate diet-induced emotional and metabolic disturbances, thereby underscoring the importance of nutrition during critical developmental periods.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111300"},"PeriodicalIF":3.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-12DOI: 10.1016/j.brainresbull.2025.111301
Jing Zhang , Tianjuan Ju , Yaru Qin, Ming Hou, Lei Gao, Li-an Wu
P2X receptors (P2XRs), membrane ion channels activated by extracellular adenosine 5’ -triphosphate (ATP), play a pivotal role in nociception by directly promoting pain signaling. Currently, antagonists targeting P2XRs have taken effect in alleviating various pain. The therapeutic potential of the P2X receptor family has become a central focus. Consequently, numerous research groups and pharmaceutical companies are actively engaged in developing novel P2XR antagonists. Furthermore, an increasing number of clinical trials on P2XR antagonists have obtained encouraging results. This review provides an overview of the structural characteristics and cellular localization of P2XRs, their molecular mechanisms and signaling pathways implicated in orofacial pain. Additionally, it explores the development of P2XR antagonists and their therapeutic application for managing orofacial pain. In conclusion, this review highlights the promising role of P2XRs as therapeutic targets for orofacial pain treatment.
{"title":"Therapeutic targeting of P2X receptors for orofacial pain","authors":"Jing Zhang , Tianjuan Ju , Yaru Qin, Ming Hou, Lei Gao, Li-an Wu","doi":"10.1016/j.brainresbull.2025.111301","DOIUrl":"10.1016/j.brainresbull.2025.111301","url":null,"abstract":"<div><div>P2X receptors (P2XRs), membrane ion channels activated by extracellular adenosine 5’ -triphosphate (ATP), play a pivotal role in nociception by directly promoting pain signaling. Currently, antagonists targeting P2XRs have taken effect in alleviating various pain. The therapeutic potential of the P2X receptor family has become a central focus. Consequently, numerous research groups and pharmaceutical companies are actively engaged in developing novel P2XR antagonists. Furthermore, an increasing number of clinical trials on P2XR antagonists have obtained encouraging results. This review provides an overview of the structural characteristics and cellular localization of P2XRs, their molecular mechanisms and signaling pathways implicated in orofacial pain. Additionally, it explores the development of P2XR antagonists and their therapeutic application for managing orofacial pain. In conclusion, this review highlights the promising role of P2XRs as therapeutic targets for orofacial pain treatment.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111301"},"PeriodicalIF":3.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-12DOI: 10.1016/j.brainresbull.2025.111299
AnaLee Shaw , Rujia Teng , Toluwani Fasina , Ana-Sofia Gonzales , Audrey Wong , Daniel Schweitzer , Isaac Oluwatobi Akefe
Delirium is a complex medical condition marked by acute episodes of cognitive dysfunction and behavioral disturbances, with a multifaceted etiology and challenging management across various clinical settings. Older adults, particularly in postoperative contexts, are at increased risk of developing delirium. Despite extensive research, a single underlying pathophysiological mechanism for delirium remains elusive. However, emerging evidence suggests a correlation between lipid dysregulation and delirium development in elderly patients, especially in postoperative settings. This connection has led to proposed treatments targeting dyslipidemia and associated neuroinflammatory effects in acute-phase delirium. This review aims to synthesize current literature on the relationship between lipid dysregulation and delirium in older adults, highlighting the need for further research into specific neurolipidome constituents and age-related lipid profile changes, potentially uncovering novel therapeutic strategies for delirium.
{"title":"Lipid dysregulation and delirium in older adults: A review of the current evidence and future directions","authors":"AnaLee Shaw , Rujia Teng , Toluwani Fasina , Ana-Sofia Gonzales , Audrey Wong , Daniel Schweitzer , Isaac Oluwatobi Akefe","doi":"10.1016/j.brainresbull.2025.111299","DOIUrl":"10.1016/j.brainresbull.2025.111299","url":null,"abstract":"<div><div>Delirium is a complex medical condition marked by acute episodes of cognitive dysfunction and behavioral disturbances, with a multifaceted etiology and challenging management across various clinical settings. Older adults, particularly in postoperative contexts, are at increased risk of developing delirium. Despite extensive research, a single underlying pathophysiological mechanism for delirium remains elusive. However, emerging evidence suggests a correlation between lipid dysregulation and delirium development in elderly patients, especially in postoperative settings. This connection has led to proposed treatments targeting dyslipidemia and associated neuroinflammatory effects in acute-phase delirium. This review aims to synthesize current literature on the relationship between lipid dysregulation and delirium in older adults, highlighting the need for further research into specific neurolipidome constituents and age-related lipid profile changes, potentially uncovering novel therapeutic strategies for delirium.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111299"},"PeriodicalIF":3.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-11DOI: 10.1016/j.brainresbull.2025.111295
Yihao Guo , Tao Liu , Huijuan Chen , Liangdong Zhou , Weiyuan Huang , Kun Zhang , Xiaoyi Wang , Yi wang , Juan Helen Zhou , Feng Chen , for the Alzheimer’s Disease Neuroimaging Initiative
Background
Diffusion-tensor image analysis along the perivascular space (ALPS) index that has the potential to reflect brain interstitial fluid (ISF) dynamics may predict the development of Alzheimer’s Disease (AD). We aimed to study whether brain ISF dynamics indicated by the ALPS index relate to AD dementia diagnosis and AD-related changes.
Methods
This study included a discovery cohort (n = 180) and a validation cohort (n = 127), which were composed of cognitively normal, subjective memory concern, mild cognitive impairment, and AD dementia subjects. All participants underwent brain magnetic resonance imaging examination and neuropsychological evaluation. The diffusivities and diffusion-tensor image analysis along the perivascular space (ALPS) were calculated. The support vector machine (SVM) model for AD dementia diagnosis was built in the discovery cohort and validated in the validation cohort. Linear mixed-effects models were used to evaluate the association between the ALPS and cognitive decline. Cox regression models were used to evaluate the association between the ALPS and the risk of AD dementia.
Results
There was a lower median ALPS index in the AD dementia group compared to other groups (all P < 0.05) for both cohorts. The SVM model for AD dementia diagnosis produced an AUC of 0.802 in the discovery cohort (P < 0.001) and 0.783 in the external validation cohort (P < 0.001). Higher ALPS levels were associated with less cognitive decline (P < 0.001). Moreover, lower baseline ALPS had a greater risk of converting to AD dementia (P = 0.014).
Conclusions
The SVM model based on diffusivities and ALPS was effective for AD dementia diagnosis, and higher ALPS levels are associated with a lower risk of AD-related changes. These findings suggest that ALPS may provide a useful AD progression or treatment biomarker.
{"title":"Decreased brain interstitial fluid dynamics is associated with risk of Alzheimer’s disease-related cognitive decline","authors":"Yihao Guo , Tao Liu , Huijuan Chen , Liangdong Zhou , Weiyuan Huang , Kun Zhang , Xiaoyi Wang , Yi wang , Juan Helen Zhou , Feng Chen , for the Alzheimer’s Disease Neuroimaging Initiative","doi":"10.1016/j.brainresbull.2025.111295","DOIUrl":"10.1016/j.brainresbull.2025.111295","url":null,"abstract":"<div><h3>Background</h3><div>Diffusion-tensor image analysis along the perivascular space (ALPS) index that has the potential to reflect brain interstitial fluid (ISF) dynamics may predict the development of Alzheimer’s Disease (AD). We aimed to study whether brain ISF dynamics indicated by the ALPS index relate to AD dementia diagnosis and AD-related changes.</div></div><div><h3>Methods</h3><div>This study included a discovery cohort (n = 180) and a validation cohort (n = 127), which were composed of cognitively normal, subjective memory concern, mild cognitive impairment, and AD dementia subjects. All participants underwent brain magnetic resonance imaging examination and neuropsychological evaluation. The diffusivities and diffusion-tensor image analysis along the perivascular space (ALPS) were calculated. The support vector machine (SVM) model for AD dementia diagnosis was built in the discovery cohort and validated in the validation cohort. Linear mixed-effects models were used to evaluate the association between the ALPS and cognitive decline. Cox regression models were used to evaluate the association between the ALPS and the risk of AD dementia.</div></div><div><h3>Results</h3><div>There was a lower median ALPS index in the AD dementia group compared to other groups (all <em>P</em> < 0.05) for both cohorts. The SVM model for AD dementia diagnosis produced an AUC of 0.802 in the discovery cohort (<em>P</em> < 0.001) and 0.783 in the external validation cohort (<em>P</em> < 0.001). Higher ALPS levels were associated with less cognitive decline (<em>P</em> < 0.001). Moreover, lower baseline ALPS had a greater risk of converting to AD dementia (<em>P</em> = 0.014).</div></div><div><h3>Conclusions</h3><div>The SVM model based on diffusivities and ALPS was effective for AD dementia diagnosis, and higher ALPS levels are associated with a lower risk of AD-related changes. These findings suggest that ALPS may provide a useful AD progression or treatment biomarker.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111295"},"PeriodicalIF":3.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-11DOI: 10.1016/j.brainresbull.2025.111294
Peng Lai , Xingyao Chen , Jiacheng Liu , Zilei Tian , Yangke Mao , Chenyang Jia , Siting Ma , Deliang Zhu , Ming Xin , Fang Zeng , Shirui Cheng
Background
Resting-state functional magnetic resonance imaging (fMRI) studies have shown abnormal functional connectivity (FC) of the insula (INS) in patients with musculoskeletal pain (MSP). However, there is a lack of consistency in previous studies, which is an obstacle to understanding the underlying neuropathology of MSP.
Method
Seven databases, including PubMed, Web of Science, the Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chongqing VIP, were systematically searched from inception to 15 May 2024. The meta-analysis of the aberrant INS-based FC in MSP patients was performed using the anisotropic effect-size signed differential mapping (AES-SDM).
Results
A total of eleven neuroimaging studies with 276 patients and 253 HCs were included in the meta-analysis. The results indicate that MSP patients have increased FC between INS and the right median cingulate gyri, right inferior frontal gyrus, right paracentral lobule, and right supplementary motor area, and decreased FC between INS and the right posterior cingulate gyrus, left precuneus, and left angular gyrus. Heterogeneity and sensitivity analysis showed that most of the results of INS-based FC were highly reproducible and robust. Meta-regression analysis showed that revealed a negative association between the Visual Analog Scale (VAS) score and the reduction in FC between the INS and the left precuneus.
Conclusion
The meta-analysis reveals that patients with MSP show abnormal FC between the INS and multiple brain regions, which are involved in emotional, cognitive, sensory, visuospatial and motor regulation of pain. These findings provide important insights into the underlying neuropathological mechanisms of musculoskeletal disorders.
{"title":"Abnormalities of insular functional connectivity in patients with musculoskeletal pain: A meta-analysis of resting-state fMRI studies","authors":"Peng Lai , Xingyao Chen , Jiacheng Liu , Zilei Tian , Yangke Mao , Chenyang Jia , Siting Ma , Deliang Zhu , Ming Xin , Fang Zeng , Shirui Cheng","doi":"10.1016/j.brainresbull.2025.111294","DOIUrl":"10.1016/j.brainresbull.2025.111294","url":null,"abstract":"<div><h3>Background</h3><div>Resting-state functional magnetic resonance imaging (fMRI) studies have shown abnormal functional connectivity (FC) of the insula (INS) in patients with musculoskeletal pain (MSP). However, there is a lack of consistency in previous studies, which is an obstacle to understanding the underlying neuropathology of MSP.</div></div><div><h3>Method</h3><div>Seven databases, including PubMed, Web of Science, the Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chongqing VIP, were systematically searched from inception to 15 May 2024. The meta-analysis of the aberrant INS-based FC in MSP patients was performed using the anisotropic effect-size signed differential mapping (AES-SDM).</div></div><div><h3>Results</h3><div>A total of eleven neuroimaging studies with 276 patients and 253 HCs were included in the meta-analysis. The results indicate that MSP patients have increased FC between INS and the right median cingulate gyri, right inferior frontal gyrus, right paracentral lobule, and right supplementary motor area, and decreased FC between INS and the right posterior cingulate gyrus, left precuneus, and left angular gyrus. Heterogeneity and sensitivity analysis showed that most of the results of INS-based FC were highly reproducible and robust. Meta-regression analysis showed that revealed a negative association between the Visual Analog Scale (VAS) score and the reduction in FC between the INS and the left precuneus.</div></div><div><h3>Conclusion</h3><div>The meta-analysis reveals that patients with MSP show abnormal FC between the INS and multiple brain regions, which are involved in emotional, cognitive, sensory, visuospatial and motor regulation of pain. These findings provide important insights into the underlying neuropathological mechanisms of musculoskeletal disorders.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111294"},"PeriodicalIF":3.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-10DOI: 10.1016/j.brainresbull.2025.111296
Suad Hamdan Almasoudi , Hayder M. Al-kuraishy , Ali I. Al-Gareeb , Duaa Eliwa , Athanasios Alexiou , Marios Papadakis , Gaber El-Saber Batiha
Alzheimer's disease (AD) is the chief cause of dementia and related mortality worldwide due to progressive accumulation of amyloid peptide (Aβ) and hyperphosphorylated tau protein. These neuropathological changes lead to cognitive impairment and memory dysfunction. Notably, most Food drug Administration (FDA) approved anti-AD medications such as tacrine and donepezil are engaged with symptomatic relief of cognitive impairment but do not reverse the underlying AD neuropathology. Therefore, searching for new anti-AD is advisable. It has been shown that the inflammatory signaling pathways such as mitogen-activated protein kinases (MAPK) are intricate with the Aβ and tau protein neuropathology in AD. In addition, inhibition of brain MAPK plays a critical role in mitigating cognitive dysfunction in early-onset AD. Though, the fundamental mechanisms for the beneficial effects of MAPK inhibitors were not fully explained. Therefore, this review aims to discuss the potential molecular mechanisms of MAPK inhibitors in AD.
{"title":"Role of mitogen-activated protein kinase inhibitors in Alzheimer's disease: Rouge of brain kinases","authors":"Suad Hamdan Almasoudi , Hayder M. Al-kuraishy , Ali I. Al-Gareeb , Duaa Eliwa , Athanasios Alexiou , Marios Papadakis , Gaber El-Saber Batiha","doi":"10.1016/j.brainresbull.2025.111296","DOIUrl":"10.1016/j.brainresbull.2025.111296","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is the chief cause of dementia and related mortality worldwide due to progressive accumulation of amyloid peptide (Aβ) and hyperphosphorylated tau protein. These neuropathological changes lead to cognitive impairment and memory dysfunction. Notably, most Food drug Administration (FDA) approved anti-AD medications such as tacrine and donepezil are engaged with symptomatic relief of cognitive impairment but do not reverse the underlying AD neuropathology. Therefore, searching for new anti-AD is advisable. It has been shown that the inflammatory signaling pathways such as mitogen-activated protein kinases (MAPK) are intricate with the Aβ and tau protein neuropathology in AD. In addition, inhibition of brain MAPK plays a critical role in mitigating cognitive dysfunction in early-onset AD. Though, the fundamental mechanisms for the beneficial effects of MAPK inhibitors were not fully explained. Therefore, this review aims to discuss the potential molecular mechanisms of MAPK inhibitors in AD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111296"},"PeriodicalIF":3.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-08DOI: 10.1016/j.brainresbull.2025.111293
Junbao Liao , Huahui Chen , Yiwei Liao , Can Luo , Zhi Wang , Fan Zhang , Chuanyi Fu
Cerebral ischemia-reperfusion injury (CIRI) is a leading cause of neurological impairment in stroke, primarily correlated to oxidative stress, inflammation, and ferroptosis. This study investigates the neuroprotective effects of hirudin on CIRI, focusing on its role in modulating neuronal survival, oxidative stress, and ferroptosis markers through inhibition of CCL2. A middle cerebral artery occlusion (MCAO) model in mice and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in HT22 cells were used to simulate ischemic conditions. Hirudin significantly improved neurological function and reduced cerebral edema and infarct size in the MCAO model. In vitro, hirudin enhanced neuronal viability and reduced apoptosis in OGD/R-stimulated cells. Integrative network pharmacology and transcriptomic analysis identified CCL2 as a potential target of hirudin. Hirudin treatment suppressed CCL2 expression, which in turn reduced the TLR4/NF-κB signaling activation, thereby mitigating ferroptosis and inflammatory responses in ischemic neurons. Overexpression of CCL2 partially reversed these protective effects, underscoring its role in ischemic injury. These findings suggest that hirudin alleviates CIRI by modulating CCL2 and preventing ferroptosis, offering insights into its potential as a therapeutic agent for ischemic conditions.
{"title":"Neuroprotective effects of hirudin against cerebral ischemia-reperfusion injury via inhibition of CCL2-mediated ferroptosis and inflammatory pathways","authors":"Junbao Liao , Huahui Chen , Yiwei Liao , Can Luo , Zhi Wang , Fan Zhang , Chuanyi Fu","doi":"10.1016/j.brainresbull.2025.111293","DOIUrl":"10.1016/j.brainresbull.2025.111293","url":null,"abstract":"<div><div>Cerebral ischemia-reperfusion injury (CIRI) is a leading cause of neurological impairment in stroke, primarily correlated to oxidative stress, inflammation, and ferroptosis. This study investigates the neuroprotective effects of hirudin on CIRI, focusing on its role in modulating neuronal survival, oxidative stress, and ferroptosis markers through inhibition of CCL2. A middle cerebral artery occlusion (MCAO) model in mice and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in HT22 cells were used to simulate ischemic conditions. Hirudin significantly improved neurological function and reduced cerebral edema and infarct size in the MCAO model. In vitro, hirudin enhanced neuronal viability and reduced apoptosis in OGD/R-stimulated cells. Integrative network pharmacology and transcriptomic analysis identified CCL2 as a potential target of hirudin. Hirudin treatment suppressed CCL2 expression, which in turn reduced the TLR4/NF-κB signaling activation, thereby mitigating ferroptosis and inflammatory responses in ischemic neurons. Overexpression of CCL2 partially reversed these protective effects, underscoring its role in ischemic injury. These findings suggest that hirudin alleviates CIRI by modulating CCL2 and preventing ferroptosis, offering insights into its potential as a therapeutic agent for ischemic conditions.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"224 ","pages":"Article 111293"},"PeriodicalIF":3.5,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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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